Biochemical and haematological indicators of excessive alcohol consumption.

Discriminant function analysis was used to determine the optimum combination of haematological and biochemical tests which gave the best discrimination between hospital patients with high and low alcohol intakes. We studied 265 patients with alcohol-related disease, 133 gastroenterology outpatients drinking less than 20 g of alcohol per day, and 104 patients with a variety of non-alcoholic liver disease. Values of mean cell volume (MCV), serum bilirubin, aspartate transaminase, serum alkaline phosphatase (AP) and gamma glutamyl transferase (gamma GT), serum albumin, serum globulin, and uric acid were determined in each patient. The best discrimination between the three groups of patients was provided by a combination of mean corpuscular volume, log10 gamma GT, and log10 serum alkaline phosphatase. In women, 92% of the high alcohol group, 100% of the low alcohol group, and 87% of the non-alcoholic liver disease were correctly allocated by the discriminant analysis. The corresponding figures for the men were 80%, 100%, and 71%. Thus, over 80% of patients with excessive alcohol intake were correctly allocated by the use of three simple laboratory tests.     

Preliminary study of indocyanine green clearance in primary biliary cirrhosis

Indocyanine green clearance was measured in 23 symptomatic patients with primary biliary cirrhosis who were followed up for 6 months. Ten patients either died (n = 4) from their primary biliary cirrhosis or underwent liver transplantation (n = 6) during the follow-up period. Indocyanine green clearance and other liver function test results were compared between the survivors (n = 13) and those who had died or undergone transplantation (n = 10). Indocyanine green clearance, bilirubin, bile acids, albumin, and prothrombin ratio differed significantly between the two groups, whereas age, alkaline phosphatase, globulin, and aspartate aminotransferase did not. Indocyanine green clearance gave better discrimination between the two groups than the other liver function tests, including bilirubin. There was a close correlation between indocyanine green clearance and bilirubin in patients who died or were transplanted. Further studies are necessary to define whether indocyanine green clearance is clinically useful in selecting patients for transplantation and in the timing of intervention.     

Prognostic significance of serum bile acids in cirrhosis

The value of serum bile acid concentrations for predicting prognosis in cirrhotics was compared with the prognostic significance of clinical and laboratory findings in a prospective 1-year study of 76 patients with cirrhosis. A commercial radioimmunoassay for total serum-conjugated primary bile acids was used. Of 76 patients, 16 died within the follow-up period. The concentration of bile acids in serum more closely correlated with mortality in cirrhosis than the commonly used clinical and laboratory parameters such as the Number Connection Test, ascites, albumin, pseudocholinesterase, bilirubin, prothrombin time and nutritional state. Serum bile acids alone yielded a prediction of mortality comparable to the Child classification. When logistic regression analysis was performed, optimal prediction of prognosis was achieved with the combination of serum bile acids and the Number Connection Test. Serum bile acid levels alone or in combination with the Number Connection Test may be a clinically useful prognostic index in cirrhosis.     

Prognostic significance of hepatic encephalopathy in patients with cirrhosis.

BACKGROUND: There are numerous studies concerning the natural history and prognostic factors in cirrhosis, the results of which are useful in selecting liver transplant candidates. However, little attention has been paid to the prognostic significance of hepatic encephalopathy despite the high frequency of this complication. METHODS: We reviewed the charts of 111 cirrhotic patients who developed a first episode of acute hepatic encephalopathy to determine their survival probability and to identify prognostic factors. RESULTS: During follow-up (12+/-17 months), 82 (74%) patients died. The survival probability was 42% at 1 year of follow-up and 23% at 3 years. With univariate analyses followed by a multivariate analysis, 7 out of 30 clinical and standard laboratory variables were significantly associated with poor prognosis: male sex, increased serum bilirubin, alkaline phosphatase, potassium and blood urea nitrogen, and decreased serum albumin and prothrombin activity. Patients were classified into two groups according to a prognostic index calculated from these 7 variables. Survival probability at 1 and 3 years was 73% and 38%, respectively, in patients with a low prognostic index, and 10% and 3% in patients with a high prognostic index. CONCLUSION: Hepatic encephalopathy is associated with short survival in cirrhotic patients. Although these patients can be classified into several groups with a different prognosis, the survival probability in every group is lower than that currently expected after liver transplantation. Therefore, cirrhotic patients developing a first episode of acute hepatic encephalopathy should be considered as potential candidates for this therapeutic procedure.     

Studies in obstructive jaundice

Acute obstruction of the extrahepatic ducts causes gross proximal duct dilatation, and elevated levels of ornithine carbamyl transferase, bilirubin, and alkaline phosphatase.Slow progressive obstruction causes variable proximal duct dilatation and in these cases bilirubin, alkaline phosphatase, and ornithine carbamyl transferase return to normal, despite the presence of severe though incomplete obstruction of the common duct and microscopic findings of biliary cirrhosis. In the early phases, ornithine carbamyl transferase is a slightly more sensitive indicator of biliary obstruction than alkaline phosphatase or bilirubin, but the values still return to normal in the face of a persistent stricture.If a patient who has previously had common duct surgery develops recurrent episodes of fever which suggest cholangitis, it should be assumed that he has a recurrent stricture, even though a cholangiogram and liver function may be normal or only slightly altered. A delay until the liver function studies show consistently raised levels may result in severe biliary cirrhosis and decreased hepatic reserve.     

253例乙型肝炎病毒引起的慢加急性肝衰竭预后影响因素分析

目的探讨乙型肝炎病毒引起的慢加急性肝衰竭(ACLF)患者预后的影响因素。方法根据预后将253例ACLF患者分为治疗有效组(84例)和无效组(169例),统计患者的一般资料、常规化验指标、肝功能指标和乙肝病毒学指标,回归分析各项指标与预后的关系。结果有效组和无效组性别、ALT、AST、前白蛋白、总胆固醇、血糖、AFP、血红蛋白、血小板、HBV DNA计量和e抗原(HBeAg)阳性率在两组间差异均无统计学意义(均P>0.05);有效组和无效组年龄、总胆红素水平、白蛋白、肌酐、凝血酶原活动度、纤维蛋白原和住院时间差异有统计学意义(P均<0.05)。患者年龄越大,预后越差(χ2=9.426,P<0.05)。Logistic多元回归分析表明,总胆红素、PTA、纤维蛋白原、肌酐和住院时间是ACLF的独立影响因素(P均<0.05)。结论年龄、血清总胆红素、白蛋白、肌酐、凝血酶原活动度、纤维蛋白原和住院时间影响乙型肝炎病毒引起的慢加急性肝衰竭患者的预后,其中总胆红素、PTA、纤维蛋白原、肌酐、住院时间影响显著。     

Changes of laboratory variables with time in cirrhosis: prognostic and therapeutic significance

The time change of laboratory variables in cirrhosis was studied by analysis of data from 488 patients with cirrhosis included in a controlled clinical trial of long-term prednisone vs. placebo. In the placebo group, a marked regression towards normal was seen within 3 months of entry into the trial (increase in serum albumin, acetylcholinesterase, cholesterol, hemoglobin and decrease in erythrocyte sedimentation rate). The subsequent course did not show a clear pattern, except for a slight increase in serum bilirubin and decrease in albumin. When studied in relation to the time of death in patients dying from a "hepatic" cause, marked increase in bilirubin and decrease in prothrombin index, albumin and cholesterol were seen in the year prior to death with little change before that time. In the prednisone group, a more marked decrease in bilirubin, SGOT, alkaline phosphatase, gamma-globulin, sulfobromophthalein retention, erythrocyte sedimentation rate and increase in leukocytes, prothrombin index and cholesterol were seen during the first 3 months. In relation to time of death from a "hepatic" cause, similar changes were seen as in the placebo group except that alkaline phosphatase increased and cholesterol did not decrease. A beneficial effect of prednisone on survival, as expressed by a previously developed therapeutic index, was associated with decrease in SGOT, alkaline phosphatase and gamma-globulin within the first 3 months. An increase in SGOT during prednisone seemed to be associated with harmful effects of therapy.     

Serum and Ascitic Levels of Soluble Intercellular Adhesion Molecule-1 in Patients with Alcoholic Liver Cirrhosis: Relation to Biochemical Markers of Disease Activity and Alcohol Intake

The overexpression of intercellular adhesion molecule-1 (ICAM-1) has been shown to be involved in the pathogenesis of various necro-inflammatory diseases, including alcoholic hepatitis. Shedding of this molecule from cell surfaces results in a circulating form, soluble CAM-1 (SICAM-1). In this work, the serum and ascitic concentrations of SICAM-1 were studied in relation to clinical and laboratory data in patients with alcoholic liver cirrhosis of different disease activities. Elevated circulating concentrations of this adhesion molecule were found in all cirrhotic patients, the highest in those with superimposed sewere alcoholic hepatitis, and the levels in regularly drinking cirrhotics without severe alcoholic hepatitis were likewise significantly higher than in those who had stopped drinking. The serum SICAM-1 concentration was best related to the serum AST activity, and also exhibited significant correlations with the pro-thrombin activity, serum bilirubin, albumin, peripheral leukocyte count, Maddrey's discriminant function value, Child grading, and antecedent alcohol consumption. Multivariate regression analysis revealed that the serum AST and prothrombin activities were independent predictors of the circulating SICAM-1 concentration. The concentration of SICAM-1 in the uninfected ascitic fluid of cirrhotics was about seven times lower than that in the serum; the ratio of its ascitic and serum levels was lower than that of the ascitic and serum total protein concentrations. These data contradict a significant in-traperitoneal production of the molecule. It is concluded that the serum SICAM-1 level may be useful as a marker for the current disease activity (the severity of underlying acute necroinflammatory reactions) in alcoholic liver cirrhosis.     

Endotoxemia, Encephalopathy, and Mortality in Cirrhotic Patients

Endotoxemia without sepsis was detected with a chromogenic Limulus assay in 36 of 39 (92.3%) cirrhotic patients and was absent in seven healthy volunteers. In 11 patients who underwent elective portasystemic shunt, portal vein endotoxemia was higher than inferior vena caval: p less than 0.05, systemic endotoxin levels did not change, compared to preoperative levels, on the 1st, 2nd, and 3rd postoperative days, attendant to an uneventful recovery. In 21 patients in hepatic encephalopathy after esophagogastric hemorrhage, systemic endotoxemia was higher than in well-compensated cirrhotics: p less than 0.001; it was higher in deep than in light coma: p less than 0.05; it was higher in those who died than in those who survived: p less than 0.001. Endotoxin levels showed a positive correlation with serum bilirubin: r = 0.59, p less than 0.001, and a negative correlation with prothrombin activity: r = -0.59, p less than 0.001. These data show endotoxemia without sepsis is a constant finding in cirrhosis and increasing levels of endotoxemia are associated with hepatic failure, encephalopathy, and death.     

High serum alkaline phosphatase level revealing a liver adenoma

A 25-year-old woman had a high serum level of alkaline phosphatase activity (2571 UI/L). Serum levels of transaminases, gamma glutamyl transferase and bilirubin were normal. Abdominal ultrasonography revealed a tumor nodule in the right liver lobe. There was no evidence of biliary obstruction. The serum activity of alkaline phosphatase returned to normal after surgical removal of the liver tumor. Histologic examination showed that the tumor was a liver adenoma with no evidence of degeneration. The adenoma cells reacted strongly positive to alkaline phosphatase by histochemical staining. The production of hepatic and biliary type alkaline phosphatase by the tumor is the most likely mechanism for the high serum levels observed in this patient.     

血清CA199与胆管结石及胆管炎的关系

目的 研究胆管结石合并胆管炎患者血清糖类抗原CA199水平与胆红素及肝酶谱之间的关系,探讨胆管结石并胆管炎患者血清CA199升高的原因及临床意义.方法 以350例胆管结石合并胆管炎患者为病例组,350例健康体检者为对照组,回顾性分析患者的血清CA199水平,用SPSS统计软件分析血清CA199水平与血清胆红素及肝酶谱水平之间的关系.结果 病例组患者血清CA199水平明显高于健康对照组;病例组血清CA199与血清总胆红素、直接胆红素、碱性磷酸酶、γ-谷氨酰转移酶之间呈正相关,与谷丙转氨酶、谷草转氨酶之间无相关;病例组中胆管梗阻解除及炎症控制后CA199水平明显下降.结论 胆管结石、胆管炎是造成血清CA199水平升高的原因之一,治疗前后动态观察CA199水平变化有助于良恶性疾病鉴别.     

Duodenal erosions and ulcers in patients with pancreatobiliary obstruction

In order to determine whether obstructive pancreatobiliary lesions increase the risk of duodenal erosions and ulcers, the duodenal mucosa of patients with these lesions were prospectively examined before endoscopic retrograde cholangiopancreatography (ERCP). During the study period, 133 patients underwent ERCP for various reasons in the Department of Medicine, The Aga Khan University Hospital. One hundred and twenty-three patients were eligible for final analysis. Sixty-five patients with bilirubin ≥ 35 μmol/L and alkaline phosphatase ≥ 2.5 times normal levels along with radiological evidence of pancreatobiliary obstruction were included in the obstruction group. Fifty-eight patients who did not fulfil these criteria were used in the control group. Acid peptic lesions, which included erosions and ulcers, were seen in 16 patients of the obstruction group and four patients of the control group (P=0.016, odds ratio (OR) = 4.41). Patients with carcinoma of the pancreas had a greater number of lesions than the rest of the obstruction group (P= 0.001, OR=8.75). Individual variables like age, sex, serum bilirubin, alanine aminotransferase, alkaline phosphatase, amylase levels, and duration of jaundice did not increase the vulnerability to acid peptic injury. The degree of obstruction multiplied by duration of jaundice (alkaline phosphatase x days) increased the susceptibility for duodenal disease (P=0.047). From this data it was concluded that patients with obstructive pancreatobiliary lesions are more prone to acid peptic duodenal lesions.     

Serum triiodothyronine and other clinical and laboratory indices of alcoholic liver disease.

Admission serum triiodothyronine (T3) values in 124 patients hospitalized for alcoholic liver disease were correlated with clinical and laboratory indices of liver function and commonly used determinants of thyroid function. Patients with low admission serum T3 levels had significant alterations in serum albumin, bilirubin, prothrombin time, and alkaline phosphatase associated with clinical signs of portal hypertension and collateral circulation, with little difference in serum glutamic-oxaloacetic transaminase, serum gamma glutamyl transpeptidase, or serum ornithine carbamyl transferase. This group also had a significant decrease in free T3 index despite an increase in T3 uptake; the slight reduction in total thyroxine (T4) was associated with an increase in free T4 index and no change in serum thyrotropin (TSH). For patients with alcoholic liver disease, low admission serum T3 and free T3 index values when accompanied by normal serum T4, free T4 index, and TSH levels appear to be indicative of severe liver dysfunction and increased mortality risk.     

Long-term follow-up of patients with primary biliary cirrhosis on colchicine therapy

We followed up a group of patients with primary biliary cirrhosis who participated in a 4-yr prospective, double-blind controlled trial of colchicine therapy for 4 additional years. All were placed on open label colchicine (0.6 mg twice daily) after the trial was concluded. Of the original group of 28 patients treated with colchicine, 8 died and 5 received transplants (3 of the 5 died). Of the original placebo control group eight patients died and six received transplants (1 of the 6 died). Surviving patients on long-term colchicine therapy (mean period = 8.1 yr, range = 5.3 to 9.1) showed reduction of mean serum alkaline phosphatase from 5.1 times the upper limit of normal values to 1.9 times (p less than 0.01). Mean ALT fell from 1.8 to 1.2 times the upper limit of normal (p = 0.05), and mean serum total bilirubin remained stable (1.6 mg/dl vs. 1.5 mg/dl). Major complications of cirrhosis developed in four patients in the colchicine group and five patients in the original control group. The only side effect of colchicine was diarrhea, which was noted in three patients. The diarrhea resolved with reduction in the dose of colchicine. Colchicine is a safe and inexpensive drug for the long-term treatment of primary biliary cirrhosis. The biochemical parameters of disease activity (alkaline phosphatase and ALT) remain improved after long-term follow-up, and bilirubin values remain stable. However, complications of cirrhosis, deaths and transplantations were not prevented. The clinical usefulness of colchicine in the treatment of primary biliary cirrhosis seems to be limited.     

Hepatic dysfunction in the adult respiratory distress syndrome

Multiple organ system failure is a major cause of mortality in the adult respiratory distress syndrome (ARDS). We serially evaluated parameters of multiple organ function in 24 patients during the first week after the diagnosis of ARDS and related them to outcome. The adult respiratory distress syndrome was associated with sepsis (n = 16), postoperation (n = 7), and trauma (n = 1). Fourteen of the 24 patients (58 percent) died. Although there were no significant differences in the indices of pulmonary or renal dysfunction between survivors and nonsurvivors, evidence of hepatic dysfunction was different in the two groups. On the day we identified ARDS, serum bilirubin was 1.2 mg/dl +/- 0.9 mg/dl in patients who survived, and was 2.3 mg/dl +/- 2.8 mg/dl (chi +/- SD) in those who died. Initial serum glutamic oxalacetic transaminase (SGOT) and alkaline phosphatase levels were lower in survivors than in those who died (71 +/- 44 IU/L vs 399 +/- 807 IU/L, and 121 +/- 53 IU/L vs 269 +/- 243 IU/L, respectively). These abnormalities persisted during the first week of respiratory failure, with significant differences in serum bilirubin and alkaline phosphatase between survivors and nonsurvivors (p less than 0.01). The degree of pulmonary and renal dysfunction was similar in both groups. These data suggest that liver function may be a major determinant of survival in patients with the adult respiratory distress syndrome.     

The problems of adverse effects to the liver of alpha-methyldopa]

In 20 patients who were treated with alpha-methyldopa since at least one year the bilirubin content, the activities of aspartate and alanine-aminotransferase, alkaline phosphatase and gamma-glutamyl transpeptidase as well as the retention of bromsulphalein were determined. In altogether 10 patients pathological findings of laboratory examinations were the result. The gamma-glutamyl transpeptidase activity proved to be particularly sensitive. By means of biopsy in 3 of these patients a fatty degeneration of the liver in stage I and in 4 of them a fatty degeneration of the parenchyma cell of minor degree were proved. A connection between duration and dosage of the treatment with alpha-methyldopa and these hepatological findings could not be ascertained statistically.     

Jaundice in severe bacterial infection.

Thirty patients are described who developed jaundice during the course of severe bacterial infection. Although the infecting organism was variable, as was the site of infection, the patients were generally ill and pyrexial. The group had a very high mortality rate (43%). A positive blood culture was obtained in 11 patients. Biochemical abnormalities noted were those of an increased concentration of conjugated bilirubin in the serum with only a modest increase in alkaline phosphatase and transaminase levels. Serum cholesterol was found to be normal. The mean serum urea level was significantly elevated, as were creatine phosphokinase and lactic dehydrogenase. Most patients exhibited a neutrophil leukocytosis and an elevated sedimentation rate, and the mean hemoglobin level was low. Liver histology was studied in 13 patients. There was evidence of mild bile stasis in 5 and moderate bile stasis in 2. Findings were otherwise nonspecific and were characterized by fatty change and/or inflammatory cells in the portal areas. There was no correlation between degree or duration of juandice and prognosis, although all patients who died remained jaundiced until death. It is suggested that this syndrome is not one of true cholestasis in that all biliary substances were not shown to be elevated in the serum, but that it is rather a selective defect in the excretion of conjugated bilirubin.     

Hyperfibrinolysis increases the risk of gastrointestinal hemorrhage in patients with advanced cirrhosis.

Sixty-one patients with different degrees of liver failure, 23 with Child-Pugh class B and 38 with Child-Pugh class C, were studied and observed for 3 yr. Coagulation index analysis showed significantly lower values of prothrombin activity, more prolonged activated partial thromboplastin time, higher bilirubin and fibrinogen degradation products values in class C patients. Among all patients, 28 had fibrinogen degradation products values greater than 10 micrograms/ml, and in these patients a hyperfibrinolytic state was confirmed by higher values of circulating plasminogen activator antigen (17.3 +/- 8.7 ng/ml vs. 5.41 +/- 1.9 ng/ml; p less than 0.0001) and activity (6.6 +/- 2.1 IU/ml vs. 1.92 +/- 1.12 IU/ml; p less than 0.0001) and significantly lower plasminogen activator inhibitor antigen (6.4 +/- 3.5 ng/ml vs. 15.8 +/- 5.6 ng/ml; p less than 0.0001) and activity (3.6 +/- 2.2 IU/ml vs. 8.5 +/- 3.9 IU/ml; p less than 0.0001). Patients with positive fibrinogen degradation products had higher serum bilirubin (6 +/- 4 mg/dl vs. 2 +/- 2 mg/dl; p less than 0.0001) and lower fibrinogen (156 +/- 52 mg/dl vs. 194 +/- 62 mg/dl; p less than 0.02) than patients without hyperfibrinolysis. During the follow-up period, 41 patients died, 22 from fatal gastrointestinal hemorrhage and 19 from liver failure. Thirty patients experienced fatal (22 patients) and nonfatal (8 patients) gastrointestinal hemorrhage. Patients with positive fibrinogen degradation products or class C had a higher risk of gastrointestinal bleeding than patients with negative fibrinogen degradation products (odds ratio = 8) or class B (odds ratio = 3.5), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

The differential diagnosis between intrahepatic cholestatic jaundice and viral hepatitis during pregnancy.

Clinical and laboratory findings from 15 patients with icteric viral hepatitis during pregnancy (VHP) and from 22 patients with intrahepatic cholestasis during pregnancy (CJP) were evaluated statistically in order to find out which parameters might help in order to find out which parameters might help in differentiating the two diseases. Diagnosis was established by needle liver biopsy in all cases. The following data were considered: history, physical examination, erythrocyte sedimentation rate (ESR) serum cholesterol, prothrombin time, total serum bilirubin, SGOT, SGPT, serum alkaline phosphatase, serum protein, serum flocculation tests, BSP blood clearance and serum HB Ag. Vomiting, high GOT and GPT serum levels, and serum HB Ag positivity suggest VHP diagnosis. Otherwise a severe itching with scratching lesions, high ESR, elevated total cholesterol and serum alkaline phosphatase values mainly if occurring in the later stage of pregnancy are consistent with CJP diagnosis. When clinical and laboratory data from a jaundiced pregnant female do not allow diagnosis, this can be established only on the basis of needle liver biopsy.     

Unresected colorectal liver metastases: prognostic value of laboratory variables

OBJECTIVE: To search for laboratory variables having independent prognostic signification in patients with unresected colorectal liver metastases. METHODS: We have systematically reviewed the biomedical literature using the methodology recommended by the Committee on Evidence-Based Laboratory Medicine of the International Federation of Clinical Chemistry and Laboratory Medicine, and taking into account the Consolidated Standards of Reporting Trials Statement. RESULTS: Of 644 publications retrieved, the application of strict exclusion and inclusion criteria allowed us to include only eight studies in our systematic review. The main laboratory variables evaluated in these eight studies were serum carcino-embryonic antigen, alkaline phosphatase, albumin, bilirubin, and plasma prothrombin time. None of these variables were unanimously found to have an independent prognostic significance. A meta-analysis was not possible, mainly because of heterogeneity within the primary studies and these contradictory results. CONCLUSIONS: Current evidence would not support the routine use of laboratory variables as independent prognostic variables in patients with unresected colorectal liver metastases. Taking into account the inadequate quality of the published studies, this negative conclusion might be provisory only. Until better designed studies are published, a number of arguments would support to recommend pre-treatment measurement of serum carcino-embryonic antigen and alkaline phosphatase in patients participating in clinical trials.