Alpha-L-fucosidase as a serum marker of hepatocellular carcinoma in Thailand

To evaluate the role of serum alpha-L-fucosidase (AFU) in the diagnosis of hepatocellular carcinoma (HCC), we simultaneously studied both AFU activity and alpha-fetoprotein (AFP) level in 60 patients with HCC, 60 patients with cirrhosis and chronic hepatitis each, 30 patients with other liver tumors and 60 healthy subjects. Serum AFU activity in patients with HCC (1,418.62 +/- 575.76 nmol/ml/hr) was significantly higher than that found in cirrhosis (831.25 +/- 261.13 nmol/ml/hr), chronic hepatitis (717.71 +/- 205.86 nmol/ ml/hr) or other tumors (706.68 +/- 197.67 nmol/ml/hr) and in controls (504.18 +/- 121.88 nmol/ml/hr, p < 0.05). With 870 nmol/ml/hr (mean value of controls plus 3 standard deviations) considered as the cut-off point, AFU was more sensitive (81.7 vs 39.1%) but less specific (70.7 vs 99.3%) than AFP at a level of > 400 ng/ml as a tumor marker of HCC. With both markers combined, the sensitivity was improved to as much as 82.6%. AFU activity in HCC patients was correlated to tumor size (r = 0.3529, p = 0.006) but not associated with tumor staging classified by Okuda's criteria (p = 0.1). The AFU activity in the viral hepatitis group (hepatitis B or C) was also significantly higher than in the non-viral group (p = 0.0005). We conclude AFU to be a useful marker, in conjunction with AFP and ultrasonography, for detecting HCC, particularly in patients with underlying viral hepatitis and cirrhosis.     

Killer cell (K-cell) population in chronic liver disease

Peripheral blood killer cell (K-cell) population of patients with chronic hepatitis was investigated by means of a plaque-assay method using sheep red blood cells. The mean K-cell population of 14 control subjects was 5.1 +/- 2.0% (mean +/- SD), and that of 28 patients with chronic hepatitis was 4.4 +/- 3.1%. These 28 patients were divided into three groups: CPH, CAH 2A and CAH 2B. The mean K-cell population of each group was decreased in order of the severity of the disease. Especially, that of patients with CAH 2B was a statistically significant decrease (p less than 0.01) from control subjects. In the course most patients with CAH, K-cell population did not change for three months after admission. K-cell population was observed to decrease in the patients with active stage of liver cirrhosis, but not in patients with the terminal stage of liver cirrhosis, even in hepatoma patients. It is suggested that the K-cell population may play an important role of pathogenesis of chronic hepatitis.     

Quantitation of intrinsic drug-metabolizing capacity in human liver biopsy specimens: support for the intact-hepatocyte theory.

Hepatic drug metabolism is decreased in patients with severe liver disease, but it is unclear to what extent this is due to altered hepatic blood flow or reduced intrinsic metabolic capacity. In this study we quantitated in needle-biopsy specimens the intrinsic capacity of liver tissue from 67 patients with mild liver disease (n = 36), chronic active hepatitis (n = 16) and cirrhosis (n = 15) to metabolize two model compounds in vitro. Hydroxylation of the low-extraction drug bufuralol resulted in the formation of 251 +/- 25 nmol 1'OH-bufuralol/gm wet wt/hr in mildly diseased liver tissue and was significantly (p less than 0.01) reduced in liver tissue exhibiting chronic active hepatitis (166 +/- 23 nmol/gm wet wt/hr) and cirrhosis (124 +/- 21 nmol/gm wet wt/hr). The formation rates of monoethylglycinexylidide, the main metabolite of the high-extraction drug lidocaine, varied widely and were not significantly different among the three groups. To relate the drug-metabolizing capacity to the hepatocyte content of liver tissue, morphometrical study was performed in the biopsy pieces originally submitted. The metabolic activity of each biopsy piece was then related to the fractional volume of hepatocytes it was calculated to contain. In mildly diseased liver tissue 355 +/- 35 nmol 1'OH-bufuralol/ml hepatocytes x hr or 12.4 +/- 1.0 mumol monoethylglycinexylidide/ml hepatocytes x hr- and in cirrhotic liver tissue 306 +/- 49 nmol 1'OH-bufuralol/ml hepatocytes x hr or 15.3 +/- 3.0 mumol monoethylglycinexylidide/ml hepatocytes x hr--were formed, respectively, and these differences were not significant.(ABSTRACT TRUNCATED AT 250 WORDS)     

Urinary Level of L-Fucose as a Marker of Alcoholic Liver Disease

The urinary levels of L-fucose were measured in 93 alcoholics: 20 of these were without liver disease, 57 with noncirrhotic alcoholic liver disease, and 16 with alcoholic liver cirrhosis. In addition, patients with cirrhosis due to viral infection, and healthy subjects were evaluated. The mean urinary L-fucose concentration showed significantly higher values in patients with alcoholic liver disease and alcoholic liver cirrhosis when compared with the healthy subjects or the chronic alcoholics without liver disease ( p < 0.001). The urinary L-fucose level was also significantly higher ( p < 0.001) in cases of alcoholic liver cirrhosis than in noncirrhotic alcoholic liver disease (384 ± 97 vs. 240 ± 95 μmol/g of creatinine). No difference was observed between the healthy subjects and chronic alcoholics without liver disease (143 ± 29 vs. 155 ± 60 μmol/g of creatinine). The urinary level of L-fucose was significantly higher with alcoholic cirrhosis (384 ± 97 μmol/g of creatinine) than with viral cirrhosis (265 ± 42 μmol/g of creatinine) ( p < 0.001). The measurement of urinary L-fucose may be a useful marker of alcoholic liver disease.     

Biotinidase Activity in Patients with Liver Disease

To investigate whether biotinidase deficiency may occur in liver disease, we determined biotinidase activity, biotin levels, and organic acids in patients with liver disease. Serum biotinidase activity in patients with liver disease (2.63 1.40 nmol/min/ml) was significantly lower than in the control group (5.43 1.06 nmol/min/ml). Serum biotinidase activity in decompensated liver cirrhosis (LC) and hepatoma was significantly lower than in acute viral hepatitis (AVH), chronic viral hepatitis (CVH), and compensated LC. The mean serum level of biotin in decompensated LC (1.8 0.6 μg/ml) and hepatoma (1.7 0.8μg/ml) was significantly lower than in the control group (2.5 1.0 μg/ml), and urinary excretion of biotin was increased in patients with liver disease, particularly in decompensated LC. Biotinidase activity correlated positively with serum biotin level and correlated negatively with urinary biotin level. Moreover, in four of five patients with severe liver disease the excretion of propionate, lactate, and 3-hydroxybutyrate decreased after biotin supplementation. The data for patients with severe liver disease so resembled those for late-onset multiple carboxylase deficiency that biotinidase deficiency is likely in patients with severe liver disease.     

Serum thrombopoietin levels in patients with chronic hepatitis and liver cirrhosis,and its relationship with circulating thrombocyte counts

BACKGROUND/AIMS: Thrombocytopenia in chronic liver diseases may be related to deficient production of thrombopoietin. The aim of this study was to measure serum thrombopoietin levels and to examine the relationship between serum thrombopoietin concentration, circulating platelet counts and clinical stage of the disease in patients with chronic hepatitis and liver cirrhosis. METHODOLOGY: The study included 18 patients with chronic hepatitis, 48 with liver cirrhosis and 27 healthy volunteers. Serum thrombopoietin levels were measured by enzyme-linked immunosorbent assay. Additionally, serum albumin levels, prothrombin time, circulating platelet counts and spleen volume index were determined. RESULTS: Mean serum thrombopoietin level (100.96 +/- 41.67 pg/mL) in the chronic hepatitis group was similar to that of the healthy group (97.60 +/- 43.99 pg/mL), however serum thrombopoietin levels in patients with liver cirrhosis (69.60 +/- 30.23 pg/mL) were lower than patients with chronic hepatitis and controls (p < 0.05 for both). In patients with liver cirrhosis, serum thrombopoietin levels were found to be decreased as the disease progressed (80.99 +/- 24.85 pg/mL in patients at Child-Pugh stage A, 67.92 +/- 39.37 in patients at stage B and 57.62 +/- 21.09 pg/mL in patients at stage C). Cirrhotic patients had increased prothrombin time (17.12 +/- 3.52 sec) and spleen volume index (94.38 +/- 26.48 cm2), and decreased serum albumin level (3.11 +/- 0.56 g/dL) and platelet counts (102,368 +/- 30,653/mm3) when compared to both chronic hepatitis and control groups. Thrombocytopenia was found in 31 (65%) of the patients with liver cirrhosis. In patients with liver cirrhosis, while there was a positive correlation between serum thrombopoietin and albumin levels (r = 0.36, p = 0.004), no correlation was found between platelet counts and serum thrombopoietin level, and spleen volume index. CONCLUSIONS: The findings reveal that serum thrombopoietin levels are normal in patients with chronic hepatitis, but in patients with liver cirrhosis, serum thrombopoietin levels decrease, as degree of cirrhosis progresses. The impaired production of thrombopoietin may contribute to the development of thrombocytopenia in advanced stage of liver disease.     

Hypercalcemia. A complication of advanced chronic liver disease

Hypercalcemia has not previously been recognized as a complication of advanced chronic liver disease without hepatoma. During a five-year period, 16 patients evaluated in the liver transplantation program at the University of Pittsburgh developed hypercalcemia. All had advanced chronic liver disease with mean total bilirubin concentration of 29.5 +/- 4.6 mg/dL (50.1 +/- 78.2 mumol/L) (mean +/- SEM) and prothrombin time 16.8 +/- 0.8s. The highest serum calcium level was 17.2 mg/dL (4.3 mmol/L). The mean serum calcium level was 11.7 +/- 0.3 mg/dL (2.93 +/- 0.075 mmol/L) with an ionized calcium level of 5.41 +/- 0.35 mg/dL (1.35 +/- 0.088 mmol/L) and a phosphorus level of 4.2 +/- 0.4 mg/dL (1.4 +/- 0.1 nmol/L). Mild to moderate renal insufficiency was present in 14 (87%) patients; the mean serum creatinine level was 2.8 +/- 0.4 mg/dL (247 +/- 35 mumol/L). In five (38%) patients parathyroid hormone was completely suppressed and in an additional five (38%) patients, it was in a range most compatible with nonhyperparathyroid hypercalcemia. The 25-hydroxyvitamin D or 1,25-dihydroxyvitamin D levels were normal or low in the 11 patients in whom determinations were made. Hypercalcemia that is not due to hyperparathyroidism or hypervitaminosis D is a potential complication of advanced chronic liver disease.     

肝病患者血清肉碱水平的临床研究

目的观察肝病患者血清肉碱水平,探讨其临床意义,为肉碱治疗肝病提供依据。方法用酶循环法检测25例急性病毒性肝炎,34例慢性病毒性肝炎,22例肾功能正常及9例肾功能异常的肝炎后肝硬化患者血清游离肉碱水平,并分别与40名正常人的检测值比较。结果血清游离肉碱:正常人为(48．3±10．2)μmol／L;急性病毒性肝炎患者为(35．2±13．2)μmol／L,明显低于正常对照组,P=0．000。慢性病毒性肝炎患者为(36．5±9．9) μmol／L,明显低于正常对照组,P=0．000。肾功能正常的肝炎后肝硬化患者为(45．0±11．0)μmol／L,比正常对照组略有下降,但差异无统计学意义,P=0．232。肾功能异常的肝炎后肝硬化患者为(83．6±50.4)μmol／L,比正常对照组升高,但差异无统计学意义,P=0．069。结论肝病患者可发生肉碱代谢异常,肝脏疾病是导致继发性肉碱缺乏的原因之一。     

Serum concentrations of the carboxyterminal cross-linking domain of procollagen type IV (NC1) and the aminoterminal propeptide of procollagen type III (PIIIP) in chronic liver disease

Serum concentrations of both the carboxyterminal cross-linking domain (NC1) of procollagen type IV and the aminoterminal propeptide of procollagen type III (PIIIP) were measured by specific radioimmunoassays in 60 patients with chronic liver disease and 50 healthy controls. Compared with controls (5.3 +/- 1.3 ng/ml, mean +/- S.D.), NC1 concentrations were significantly elevated in patients with chronic active hepatitis (10.2 +/- 2.0 ng/ml) and liver cirrhosis (13.5 +/- 3.0 ng/ml), but not in chronic persistent hepatitis (6.0 +/- 0.9 ng/ml). The concentrations in patients with active liver cirrhosis were significantly higher than those in patients with inactive cirrhosis. Serum concentrations of PIIIP in controls, parients with chronic persistent hepatitis, chronic active hepatitis and cirrhosis were 5.8 (4.3-7.9), 5.3 (3.5-7.9), 17.5 (10.6-28.9), 16.7 (10.4-26.7) ng/ml, respectively (logarithmic mean and range of mean +/- S.D. after retransformation). Patients with liver cirrhosis had significantly higher concentrations of NC1 in serum than those with chronic active hepatitis, but there was no difference in serum PIIIP concentrations between the two groups. These data suggest an alteration of type IV collagen metabolism in chronic liver disease. In liver cirrhosis, the metabolism of collagen IV is apparently different from that of collagen type III; serum NC1 determinations may therefore provide additional information on chronic liver disease, particularly in patients with cirrhosis with a normal level of serum PIIIP. Further follow-up studies as well as investigations related to the basic mechanism of the elevation of these peptides in serum are needed in order to understand their clinical significance fully.     

Evaluation of plasma thrombomodulin (TM) levels in patients with liver disease]

Plasma TM levels in patients with various liver diseases were determined by using EIA. In normal subject (n = 58), it's concentration was 15.9 +/- 3.5 ng/ml (mean +/- SD). In liver diseases, the level increased: Acute hepatitis (n = 16), 23.0 +/- 6.5, chronic active hepatitis (n = 21) 22.2 +/- 6.6, compensated liver cirrhosis (n = 20) 27.8 +/- 10.1, decompensated liver cirrhosis (n = 14) 47.6 +/- 17.5, compensated liver cirrhosis with hepatocellular carcinoma (n = 7) 26.3 +/- 7.9, decompensated liver cirrhosis with hepatocellular carcinoma (n = 4) 46.0 +/- 11.8, and fulminant hepatitis (n = 9) 42.0 +/- 20.4. The percentages of abnormal values higher than 22.9 ng/ml, which is mean + 2SD in control subject was 38-100% in liver diseases, especially 100% in patients with liver cirrhosis or with fulminant hepatitis. There was little correlation between plasma TM levels and conventional liver function tests in various liver diseases. Immunohistochemical study of liver tissue showed that an increase of plasma TM level was partially caused by damage and regeneration of endothelial cell. Based on these results the measurement of plasma TM concentration could be an useful marker for detection of hepatic failure.     

Changes of Splanchnic Circulation with Progression of Chronic Liver Disease Studied by Echo-Doppler Flowmetry

Changes that occurred in splanchnic circulation with the progression of chronic liver disease were investigated using an ultrasonic Doppler flowmeter in healthy adults and in patients with chronic active hepatitis and liver cirrhosis in the supine position after an overnight fast. Superior mesenteric venous flow, splenic venous flow, and portal venous flow were significantly increased in patients with liver cirrhosis but not in patients with chronic active hepatitis compared with normal subjects. Portal venous flow (control value 10.5 +/- 2.3 ml/min/kg body weight) minus the sum of superior mesenteric venous flow and splenic venous flow was 0.8 +/- 2.1 ml/min/kg body weight in the control, (0.1 +/- 1.9) in chronic active hepatitis, and (-2.2 +/- 4.3) in liver cirrhosis; the difference was significant between the control and cirrhosis groups. These results indicate that in patients with liver cirrhosis a hyperdynamic state occurs in the splanchnic circulation of the intestine and spleen and that some portion of splanchnic blood flow bypasses the liver into the systemic circulation.     

Determination of the rate of micronucleus formation in lymphocytes in liver diseases and its clinical significance

The rate of micronucleus formation in lymphocytes was determined in 42 patients (including 10 acute icteric hepatitis B, 15 chronic active hepatitis B (CAH), 8 liver cirrhosis and 9 liver cancer) and 13 normal subjects. The results showed that the rate of micronucleus formation in lymphocytes in the patients with CAH (12.267 +/- 5.298%), liver cirrhosis (12.375 +/- 8.551%) or liver cancer (19.444 +/- 13.324%) was markedly higher than that in those with acute icteric hepatitis B (5.400 +/- 1.430%) or normal subjects (3.308 +/- 1.284%) (P less than 0.01). The rate of micronucleus formation in lymphocytes is higher in the liver cancer group than that in the CAH group or cirrhosis group (P less than 0.05). The rate of presence of two or more micronuclei in the lymphocytes was obviously higher in the liver cancer group (3.667 +/- 4.743%) than that in the liver cirrhosis group (1.500 +/- 1.690%), CAH group (1.467 +/- 1.807%), acute icteric hepatitis B group (0.600 +/- 1.075%) or healthy group (0.462 +/- 0.660%) (P less than 0.01 or less than 0.05). This method is much simpler than the measurement of chromosomal damage, and its reliability is as good as the latter. Measurement of micronuclei in lymphocytes can reflect the degree of liver damage in patients with the infection of hepatitis B virus. It may be used as the subclinical marker of the patients with liver cancer too.     

Impaired splanchnic and peripheral glucose uptake in liver cirrhosis.

BACKGROUND/AIM: Patients with liver cirrhosis are insulin-resistant and frequently glucose-intolerant. Although peripheral glucose uptake has been shown to be impaired in liver cirrhosis, little is known about the significance of splanchnic (hepatic) glucose uptake after oral glucose load. METHODS/RESULTS: We performed an oral glucose tolerance test and euglycemic hyperinsulinemic clamp with oral glucose load for eight patients with liver cirrhosis and eight patients with chronic active hepatitis. The patients with liver cirrhosis had higher plasma glucose levels 2 h after glucose load than those with chronic active hepatitis (228+/-22 mg/dl vs. 102+/-9 mg/dl, p<0.01). Using the euglycemic hyperinsulinemic clamp with oral glucose load, we simultaneously measured peripheral and splanchnic glucose uptake. Peripheral glucose uptake in liver cirrhosis was 6.1+/-0.7 mg x kg(-1) x min(-1), which was lower than that in healthy volunteers (10.5+/-0.9 mg x kg(-1) x min(-1), p<0.05) and in chronic active hepatitis (8.4+/-0.3 mg x kg(-1) x min(-1), p<0.05). Furthermore, splanchnic glucose uptake in liver cirrhosis was much lower (20.1+/-3.4%) than in healthy volunteers (36.0+/-4.0%, p<0.05) and in chronic active hepatitis (37.2+/-3.1%, p<0.05). CONCLUSION: These results suggest that glucose intolerance in patients with liver cirrhosis is caused by a defect of the glucose uptake of both splanchnic and peripheral tissues.     

Serum neopterin levels in children with hepatitis-B-related chronic liver disease and its relationship to disease severity

AIM： To evaluate serum neopterin levels and their correlations with liver function tests and histological grade in children with hepatitis-B-related chronic liver disease. METHODS： The study population comprised 48 patients with chronic active hepatitis B, 32 patients with hepatitis-B-related active liver cirrhosis and 40 normal controls. Serum neopterin was measured using an enzyme-linked immunosorbent assay. RESULTS： The mean ＋ SD serum neopterin levels were 14.2 ± 5.6 nmol/L in patients with chronic hepatitis, 20.3 ± 7.9 nmol/L in patients with liver cirrhosis and 5.2 ± 1.4 nmol/L in control group. Serum neopterin levels were significantly higher in patients with chronic hepatitis （P = 0.005） and cirrhosis patients （P = 0.008）, than in control subjects. Cirrhotic patients had significantly higher serum neopterin levels than patients with chronic hepatitis （P = 0.004）. There was a positive correlation between serum neopterin levels and alanine aminotransferase levels in patients with chronic hepatitis （r = 0.41, P = 0.004） and cirrhotic patients （r = 0.39, P = 0.005）. Positive correlations were detected between serum neopterin levels and inflammatory score in patients with chronic hepatitis （r = 0.51, P = 0.003） and cirrhotic patients （r = 0.49, P = 0.001）. CONCLUSION： Our results suggest that serum neopterin levels can be considered as a marker of inflammatory activity and severity of disease in children with hepatitis-B-related chronic liver disease.     

The effect of propranolol on thyroid function in patients with liver cirrhosis

The effect of propranolol on thyroid hormones of 7 healthy subjects and 10 patients with histologically proven alcoholic liver cirrhosis was investigated. The fractions of plasma T3 and free T4 were determined by specific radioimmunoassay before and after two weeks of propranolol administration. Under basal conditions, both T3 and FT4 levels were found significantly lower in patients with cirrhosis than in healthy subjects (1.86 +/- 0.10 vs. 1.18 +/- 0.41 nmol/l, p less than 0.001; 9.31 +/- 0.41 vs. 8.17 +/- 0.91 pg/ml, p less than 0.05, respectively). In healthy subjects propranolol administration led to a significant reduction of T3 serum levels (from 1.88 +/- 0.10 to 1.51 +/- 0.12 nmol/L, p less than 0.001), while in patients with liver cirrhosis no significant changes in T3 and FT4 were found. In patients with liver cirrhosis propranolol administration did not affect thyroid hormone levels.     

Quantitative measurement of portal blood flow in patients with chronic liver disease using an ultrasonic Duplex system consisting of a pulsed Doppler flowmeter and B-mode electroscanner

Portal blood flow (PBF) can be measured quantitatively using a B-mode combined pulsed Doppler (BCD) system. This system combines a real time B-mode linear type electroscanner and a pulsed Doppler (D-mode) flowmeter. Since both modes are displayed in realtime, Doppler blood flow signals can be retrieved at will from any depth. The blood flow velocity determined by the Doppler spectrogram and the vascular cross-sectional area measured from the B-mode tomographic image enables the quantitative calculation of blood flow volume. Using this system, PBF was measured quantitatively in 88 healthy adults, 54 patients with chronic hepatitis, 65 with cirrhosis of the liver, 27 with primary hepatoma and 12 with idiopathic portal hypertension (IPH). Results of PBF volume measurement were as follows: 889 +/- 284 ml/min (mean +/- S.D.) for healthy adults, 851 +/- 237 ml/min for patients with chronic hepatitis, 870 +/- 289 ml/min for cirrhosis of the liver, 966 +/- 375 ml/min for primary hepatoma and 1,047 +/- 381 ml/min for IPH. These preliminary results demonstrated that this ultrasonic Duplex system is clinically useful to determine the quantitative amount of PBF.     

Urinary 11-dehydro-thromboxane B2: a quantitative index of platelet activation in cerebral infarction.

Thromboxane A2 (TXA2) biosynthesis was studied in healthy subjects, patients with chronic cerebral infarction, patients under chronic aspirin treatment and patients with atrial fibrillation. Urinary 11-dehydro-TXB2, as a major metabolite of TXA2, was measured by radioimmunoassay. The extent of carotid atherosclerosis was determined by B-mode ultrasonography. The mean +/- SD urinary excretion in patients with cerebral infarction and distinct carotid-atherosclerotic lesions (1,725 +/- 239 ng/g creatinine, n = 6) was significantly higher (p less than 0.01) than in healthy subjects (911 +/- 239 ng/g creatinine, n = 44) and patients with cerebral infarction who had no distinct carotid lesion (1,050 +/- 191 ng/g creatinine, n = 6). The urinary excretion of healthy subjects was higher (p less than 0.01) in smokers (1,063 +/- 244 ng/g creatinine, n = 17) than in non-smokers (815 +/- 183 ng/g creatinine, n = 27). Aspirin largely suppressed 11-dehydro-TXB2 excretion (266 +/- 114 ng/g creatinine, n = 7). Three of 5 patients with atrial fibrillation showed very high values. Our results indicated that platelet activation occurs in the atherosclerotic lesions, and that urinary 11-dehydro-TXB2 is the appropriate analytic target for detecting platelet activation.     

Calcitonin in hepatoma and cirrhosis

Plasma immunoreactive calcitonin (iCT) is elevated in primary liver cancer and its measurement has been proposed as a tumour marker. Since iCT is also frequently raised in alcoholic liver cirrhosis, it would be of practical relevance to distinguish this condition from primary hepatoma by measuring the plasma level of iCT. We measured plasma iCT levels in 23 subjects with primary liver cancer, in 27 with hepatic cirrhosis and in 42 healthy subjects who served as normal controls. A gel-chromatography analysis was carried out on the plasma of two cases of hepatoma, two of cancer and cirrhosis, and two of alcoholic liver cirrhosis. The subjects with primary liver cancer had values of plasma iCT (pg/ml; mean +/- SE) of 342 +/- 41; those with liver cirrhosis 159 +/- 22, and normal controls 73 +/- 3. The increase in primary liver cancer was significant in comparison both healthy subjects (P less than 0.001) and with cirrhotic patients (P less than 0.001). Twenty-two out of 23 patients with primary liver cancer and 13 out of 27 with liver cirrhosis had elevated iCT values (upper normal limit 113 pg/ml). There was no significant difference between plasma iCT values of patients with cancer and those with cirrhosis. However, we measured iCT values higher than 400 pg/ml only in patients with primary liver cancer. The gel-filtration analysis showed 3 or 4 peaks of iCT with a molecular weight higher than synthetic human calcitonin. The results suggest that plasma iCT levels can be considered a reliable marker of liver cancer, whereas its discriminating power between liver cancer and cirrhosis was not entirely satisfactory.(ABSTRACT TRUNCATED AT 250 WORDS)     

The aminopyrine breath test does not correlate with histologic disease severity in patients with cholestasis

To determine whether the aminopyrine breath test can be used to document the presence of cirrhosis in patients with cholestatic liver disease, 19 patients (13 primary biliary cirrhosis, 4 sclerosing cholangitis and 2 chronic extrahepatic bile duct obstruction) underwent clinical and biochemical evaluations, liver biopsies and an aminopyrine breath test. Results were compared with those in 10 patients with biopsy-proven chronic active hepatitis with bridging and/or cirrhosis and in 22 healthy subjects. The aminopyrine breath test results in the 10 cholestatic patients with cirrhosis were not significantly different from the results in precirrhotic cholestatic patients (mean +/- S.D., 11.2 +/- 5.0 vs. 11.6 +/- 2.8% dose per 2 hr, p greater than 0.05) or healthy subjects (11.5 +/- 2.9% dose per 2 hr). In contrast, the results in the patients with chronic hepatitis were markedly depressed (3.2 +/- 1.9% dose per 2 hr, p less than 0.05). The aminopyrine breath test results did not correlate with results of conventional liver function tests in the cholestatic patients. These results demonstrate that the aminopyrine breath test is not clinically useful in identifying the presence of cirrhosis in patients with cholestatic liver disease, and provide further evidence that decreased microsomal enzyme function is a late feature of cholestatic liver disease.     

Carnitine metabolism in patients with chronic liver disease

Carnitine metabolism was studied in 79 patients with chronic liver disease, including 22 patients with noncirrhotic liver disease and 57 patients with different types of cirrhosis (22 patients with hepatitis B- or C-associated cirrhosis, 15 patients with alcohol-induced cirrhosis, 15 patients with primary biliary cirrhosis [PBC], and 5 patients with cryptogenic cirrhosis), and compared with 28 control subjects. In comparison with control subjects, patients with noncirrhotic liver disease showed no change in the plasma carnitine pool, whereas patients with cirrhosis had a 29% increase in the long-chain acylcarnitine concentration. Analysis of subgroups of patients with cirrhosis showed that patients with alcohol-induced cirrhosis had an increase in the total plasma carnitine concentration (67.8 +/- 29.5 vs. 55.2 +/- 9.9 micromol/L in control subjects), resulting from increases in both the short-chain and long-chain acylcarnitine concentration. In this group of patients, the acylcarnitine concentrations showed a close correlation with the total carnitine concentration, and the total carnitine concentration with the serum bilirubin concentration. Urinary excretion of carnitine was not different between patients with noncirrhotic or cirrhotic liver disease and control patients. However, patients with PBC showed an increased urinary excretion of total carnitine (52.5 +/- 40.0 vs. 28.0 +/- 16.7 micromol carnitine/mmol creatinine), resulting from an increase in the fractional excretion of both free carnitine and short-chain acylcarnitine. The current studies show that patients with cirrhosis are normally not carnitine deficient. Patients with alcohol-induced cirrhosis have increased plasma carnitine concentrations, which may result from increased carnitine biosynthesis because of increased skeletal muscle protein turnover. The increase in the fractional carnitine excretion in patients with primary biliary cirrhosis may result from competition of bile acids and/or bilirubin with tubular carnitine reabsorption and/or from a reduced activity of the carnitine transporter located in the proximal tubule.(Hepatology 1997 Jan;25(1):148-53)