Comparison of rocket and crossed immuno-electrophoresis assays for determination of the level of actin complexing of Gc globulin.

OBJECTIVE: Gc globulin (vitamin D-binding protein) is a component of the extracellular actin scavenger system. The level of Gc globulin is reduced in patients with fulminant hepatic failure, septic shock and trauma. Furthermore, low levels of Gc globulin in patients with fulminant hepatic failure and multiple trauma have been found to correlate with the morbidity and mortality of patients. Owing to a large increase in the turnover of Gc globulin upon complex formation with actin, it may be important to determine both the total Gc globulin concentration and the degree of complexing with actin for estimating the clinical prognosis of a patient. For this reason, we have compared a crossed immuno-electrophoresis method (CIE), suitable for visualizing the degree of complexing with actin, with a rocket immuno-electrophoresis method (RIE), previously used for determination of the complex degree. MATERIAL AND METHODS: Sera from healthy donors and from patients with acetaminophen-induced liver disease or trauma were investigated using CIE, RIE and enzyme-linked immunosorbent assay (ELISA). RESULTS: Using the CIE, no Gc globulin-actin complexes were detected among healthy donors. Complexes were present in 21 of 39 patients with liver disease and 3 of 37 trauma patients. High complex ratios (> 20 %) were found in 6 of 7 patients with hepatic encephalopathy. Using the RIE, complexes were detected in most samples. CONCLUSION: The results show that the CIE method may be used for determining the degree of actin complexing in conjunction with ELISA or RIE in determining the levels of total Gc globulin.

Gc globulin (vitamin D-binding protein) levels: an inhibition ELISA assay for determination of the total concentration of Gc globulin in plasma and serum.

Gc globulin, also called vitamin D-binding protein, is a plasma protein involved in the actin-scavenger system. In this study, the total Gc globulin concentration in serum or plasma samples was determined using a new, fast, solid-phase inhibition assay. Included in the study were 228 healthy volunteers (131 M, 97 F), 22 pregnant women, 90 cancer patients and 9 patients with chronic liver disease. Moreover, the degree of complexing with actin was determined in selected samples using crossed immunoelectrophoresis. The Gc globulin level in healthy controls was in the range 176-623 mg/L, showing no age dependency. The median level was found to be significantly higher in women than in men. Gc globulin concentrations were raised during pregnancy, showing a median value of 541 mg/L in the first trimester, and slightly raised to 574 mg/L in the second trimester. Cancer patients showed no changes in Gc globulin level, and there was no sign of increased amounts of complexing with actin. Chronic liver patients showed increased levels of Gc globulin following transplantation, but no signs of complexing with actin. This new solid-phase inhibition assay is fast, it is a good complement to the existing quantification methods, and it is especially suitable for determination of the Gc globulin status in acute liver patients before and during treatment.

Influence of acute and chronic alcohol intake on the clinical course and outcome in acetaminophen overdose.

BACKGROUND: Animal studies on acetaminophen toxicity suggest that chronic alcohol intake affects the outcome adversely, whereas acute alcohol intake seems protective. Few clinical data are available. METHODS: We studied 209 consecutive patients with single-dose acetaminophen overdose. The combined influence of independent variables (gender, age, dose, delay to antidote treatment, chronic and acute alcohol intake and nomogram risk group) on dependent variables (death, development of hepatic encephalopathy and biochemical liver markers) was studied using multiple or logistic regression analysis. RESULTS: Fifty-seven (27.3%) patients had chronic alcohol intake and 45 (21.5%) patients had acute alcohol intake. Forty-four (21.1%) patients developed hepatic coma and 20 (43.5%) of these patients died. Chronic alcohol intake was significantly and independently associated with the development of hepatic coma, with a lower prothrombin index, lower platelet count, higher creatinine and higher bilirubin. The relative risks for hepatic coma and death were 5.3 (95% confidence interval, 2.2-12.4) and 1.4 (95% confidence interval, 0.5-3.9), respectively, in the chronic alcohol intake group compared with the no chronic alcohol intake group. Acute alcohol intake was not significantly associated with any of the dependent variables studied. CONCLUSIONS: Chronic alcohol intake enhances acetaminophen hepatotoxicity, whereas acute alcohol intake does not affect the clinical course.

Temporal profile of total, bound, and free Gc-globulin after acetaminophen overdose.

Low admission values of the actin scavenger Gc-globulin are associated with an adverse outcome in acetaminophen (paracetamol) overdose. This prospective longitudinal study including 84 patients with acetaminophen overdose characterizes the temporal profile of Gc-globulin during the entire length of hospitalization. Serum Gc-globulin (total, actin bound, and free) levels and actin-complex ratio were measured on admission and every 12 hours until discharge. In 32 patients without hepatotoxicity (non-HEPTOX group; peak transaminase levels < 1,000 U/L), total and free Gc-globulin levels and complex ratio remained within normal range during hospitalization. Among 52 patients with hepatotoxicity (HEPTOX group; peak transaminase levels > 1,000 U/L), 15 patients had hepatic encephalopathy (HE), and 37 patients did not. In these 2 groups, total and free Gc-globulin levels decreased to 97 and 50 mg/L and 148 and 86 mg/L, respectively (normal mean, 340 and 299 mg/L), the nadir occurring at 72 hours postoverdose. Complex ratio peaked at 60 hours at levels more than 3-fold greater than normal. Conversely, bound Gc-globulin remained within normal levels for all patients throughout the observation period. At day 2, a total Gc-globulin cutoff value of less than 120 mg/L correctly predicted HE in 75%, and a value greater than 120 mg/L correctly predicted the absence of HE in 91% of patients. In conclusion, Gc-globulin is severely stressed in patients with hepatotoxicity. Extreme values occurred at 60 to 72 hours postoverdose, a period in which Gc-globulin protection against actin toxicity may be inadequate. A total Gc-globulin level less than 120 mg/L on day 2 is a good predictor of later HE. Bound Gc-globulin is maintained at constant levels independent of total Gc-globulin levels, suggesting a balanced upregulation of the removal of bound Gc-globulin even under conditions with increased actin release.

Increased turnover of Gc-globulin in patients with hepatic encephalopathy.

BACKGROUND: A low serum level (< 100 mg/L) of the actin-scavenger Gc-globulin is a prognostic marker of non-survival in fulminant hepatic failure (FHF). It is unknown whether decreased production or increased consumption (or both) is responsible for the low Gc-globulin levels. METHODS: Ten patients with FHF and four patients with acute or chronic liver disease (AOCLD) with hepatic encephalopathy (HE) grades II-IV were included. Eight patients with cirrhosis (chronic liver disease, CLD) without HE served as controls. Total, free, and actin-bound Gc-globulin were measured in samples from an artery, a central vein, and a hepatic vein. In 12 patients (9 FHF, 3 AOCLD), concentrations were measured before and after high volume plasmapheresis (HVP). RESULTS: Total Gc-globulin was reduced to 21%, 40%, and 43% of the normal level in the FHF, AOCLD, and CLD groups, respectively, whereas bound Gc-globulin was within normal range in all patients. The Gc:actin complex ratio was increased 3.8, 2.5, and 1.9-fold compared with normal levels. Total, free, and bound serum Gc-globulin levels did not differ among arterial, systemic venous, or hepatic venous blood. Total Gc-globulin rose to >100 mg/L in all patients after HVP, whereas bound Gc-globulin remained unchanged. The Gc-globulin production rate in FHF and AOCLD patients was increased to 4.1 +/- 1.3 mg/min compared to literature values of 0.6 mg/min in healthy individuals. The estimated half-life of total Gc-globulin was shorter in the patients compared to healthy individuals (127 +/- 56 min and 870 min, respectively). CONCLUSIONS: Gc-globulin levels were reduced in patients with FHF and AOCLD because a 7-fold increase of Gc-globulin production rate could not compensate for the accelerated clearance. Bound Gc-globulin was maintained within normal levels in all circumstances studied, indicating a possible regulatory role of this parameter in the clearance of actin.

Trauma stimulates the synthesis of Gc-globulin.

OBJECTIVE: Actin is the dominating intracellular protein and is released to the circulation after tissue injury. Gc-globulin is one of the plasma proteins responsible for removal of actin from the circulation. Recent studies have shown that the level of Gc-globulin is reduced shortly after trauma. Serial changes in Gc-globulin after severe injury have not been studied so far and could provide additional information about the role of Gc-globulin in the pathophysiological response to trauma. DESIGN: Prospective, observational. SETTING: Surgical intensive care unit in a university hospital. PATIENTS: Thirty-eight patients were included in the study: 12 women and 26 men with a median age of 38 years (range 19-86) and a median Injury Severity Score (ISS) of 18 (range 6-45). Seven patients died, on day 5, 8, 8, 10, 10, 13 and 21, respectively. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The serum concentration of Gc-globulin (Gctotal) and the percentage of Gc-globulin bound to actin (Gc%complexed) were measured daily for 1 week using rocket immunoelectrophoresis. Concentrations of free Gc-globulin (Gcfree) and Gc-globulin bound to actin (Gcbound) were calculated from these analytical results. The concentration of Gctotal and Gccomplexed correlated significantly (r = -0.99, p < 0.001) throughout the time period. After day 3 levels of Gc%complexed normalised, whereas levels of Gctotal continued to increase above control values. The concentrations of Gctotal and Gcfree were significantly lower in non-survivors compared to survivors; p = 0.005 and p = 0.03, respectively. This was combined with an inverse correlation of Gcbound between these two groups (r = -0.73; p = 0.04). CONCLUSIONS: Severe injury results in a prolonged load on the extracellular actin scavenger system; more pronounced in patients who do not survive. Gc-globulin displays characteristics of an acute phase reactant, with supra-normal serum levels 1 week after severe injury. Serial measurements of Gc-globulin after trauma could prove to be a method of early identification of patients with increased risk of mortality.

Gc-globulin is an acute phase reactant and an indicator of muscle injury after spinal surgery.

OBJECTIVES AND DESIGN: Actin is the dominating protein in mammalian cells, including muscle cells, and is released into the circulation after tissue injury. Gc-globulin, one of the proteins in the Extracellular Actin Scavenger System (EASS) is responsible for the clearance of actin from the circulation. Clinical studies show that plasma levels of Gc-globulin are reduced in situations with tissue death, and that the degree of reduction correlates with development of organ dysfunction and survival. The purpose of the present study was to describe the serial changes in Gc-globulin after a standardized surgical procedure resulting in major muscle injury, comparing changes in Gc-globulin with changes in other acute phase proteins. MATERIAL AND METHODS: Twelve patients who underwent posterolateral lumbar fusion from L4 or L5 to sacrum were included in the study. Peripheral venous blood samples were obtained before surgery and on day 1, 3, 5, 12, 21, and 28 after surgery. Serum samples were analyzed for total Gc-globulin (Gc(total)), percentage of Gc-globulin complexed with actin (GC(complexed)), albumin, orosomucoid, haptoglobin, transferrin and creatin phosphokinase (CK). RESULTS: Gc(total) decreased to 87% of pre-operative values on day one. Thereafter the levels increased to a maximum of 135% of pre-operative values on day five, approaching baseline values towards the end of the observation period. Compared to this, changes in GC(complexed) displayed a mirror-like time-course, with levels of Gc(total) and GC(complexed) being significantly inversely correlated on day one (P < 0.05). Levels of albumin remained below pre-operative values the first three weeks post-operatively, reaching baseline at the end of the observation period (P < 0.05). CONCLUSION: The initial changes in Gc-globulin can be explained by increased release of actin from injured muscle tissue. Subsequently Gc-globulin displays characteristics of a so-called positive acute phase reactant, supporting previous in vitro studies, and clinical studies after minor surgery. In spite of genetic linkage and structural homology Gc-globulin and albumin are regulated differently after surgical trauma.

Admission level of Gc-globulin predicts outcome after multiple trauma.

BACKGROUND: Actin is the dominating protein in mammalian cells. Release of excessive amounts of actin into the circulation may result in a condition resembling multiple organ failure. The purpose of this study was to determine if admission levels of Gc-globulin can predict survival after multiple trauma. Also, we wanted to compare the predictive ability of Gc-globulin with that of the TRISS-Like scoring system. METHODS: Fifty-seven patients with a median ISS 18 (16-75) were included. All patients had a blood sample taken median 42 min after the injury (19-110 min). Serum Gc-globulin was measured by rocket immunoelectrophoresis. RESULTS: On admission, all patients had significantly reduced levels of Gc-globulin compared with normal controls. Gc-globulin was significantly higher in the group of survivors (n = 41), compared with non-survivors (n = 16). Median 237 mg/l vs. 188 mg/l (P < 0.01). The predictive ability of Gc-globulin regarding death was similar to that of TRISS-Like with positive predictive values of 69%, a negative predictive value of 84%, a sensitivity of 56% and a specificity of 90%. CONCLUSIONS: The predictive value of Gc-globulin regarding survival was similar to that of an established scoring system. Gc-globulin, alone or in combination with other parameters, may serve as a routine tool for early identification of patients at risk after severe injury, increasing the possibility of early intervention.

Plasma gelsolin is reduced in trauma patients.

Tissue injury results in the release of the intracellular protein actin which is cleared from the circulation by the plasma proteins gelsolin and Gc-globulin, constituting the Extracellular Actin Scavenger System (EASS). Experimental studies have shown that excessive amounts of actin in the circulation can lead to a condition resembling multiple organ dysfunction syndrome (MODS), and we have previously demonstrated that the level of Gc-globulin is decreased after severe trauma. The purpose of the present study was to determine whether the plasma levels of gelsolin were altered in the early phase after trauma. Twenty-three consecutive trauma patients were studied. Plasma samples were assayed for gelsolin by immunonephelometry with polyclonal rabbit antihuman gelsolin prepared in our own laboratory. The median time from injury until the time the first blood sample was taken was 52 min (range 20-110) and the median Injury Severity Score (ISS) was 20 (range 4-50). The gelsolin level on admission was reduced significantly in the trauma patients compared with normal controls. The median level was 51 mg/L (7-967) vs. 207 mg/L (151-621), P < 0.0001. There was no correlation between admission levels of gelsolin and ISS or survival. This study illustrates that the plasma concentration of gelsolin is significantly diminished immediately after traumatic injury. Further studies are necessary to establish a role for gelsolin or EASS in the development of MODS in trauma patients. The level of serum or plasma gelsolin can be determined rapidly and accurately using a nephelometric assay.

Prediction of hepatic encephalopathy in paracetamol overdose: a prospective and validated study.

BACKGROUND: Paracetamol overdose may cause hepatic encephalopathy (HE). This condition demands specialized care and, in some instances, liver transplantation evaluation. No model is available for predicting HE. We aimed to set up and validate a model for predicting the occurrence of HE in paracetamol overdose. METHODS: Prospectively, 161 patients with single-dose paracetamol overdose and no HE (defined as hepatic coma grade II or more) on admission were studied during a 26-month period. Patients admitted during the first 13-month period constituted a learning set to construct a model to predict the occurrence of HE. Patients admitted in the second 13-month period constituted the validation set. Serial biochemical variables (measured twice daily), the time line after the overdose, and demographic data were used for univariate testing, and significant factors were assessed in various multiple logistic regression analyses. RESULTS: Thirty-two patients (20%), 15 in the first period and 17 in the second, developed HE grade II. The best model (the highest chi-square) for HE included: log10 (hours from overdose to antidote treatment), log10 (plasma coagulation factors on admission), and platelet count hours from overdose (chi-square = 41.2, P < 0.00001). In the validation set 88% (confidence interval (CI), 64%-99%) of the patients who developed HE were correctly predicted by the constructed model, whereas 90% (CI, 79%-96%) of the patients in the non-HE group were correctly predicted. CONCLUSIONS: The constructed model for predicting HE in paracetamol overdose proved sensitive and accurate in the validation set and should be valuable for transferring high-risk patients to a liver intensive care unit/transplantation facility.

Reconstitution of the actin-scavenger system after orthotopic liver transplantation for end-stage liver disease: a prospective and longitudinal study.

Serum levels of the actin scavenger Gc-globulin (group-specific component, vitamin D-binding protein), a member of the albumin multigene family, are decreased in severe liver disease but have not been evaluated in relation to liver transplantation. We measured Gc-globulin and Gc-globulin-actin complex ratio daily for 2 weeks after transplantation in 17 patients with end-stage liver disease. Before transplantation, Gc-globulin levels were significantly less in the patients than in healthy controls (235 +/- 106 v 340 +/- 35 mg/L, respectively; P<.001), whereas complex ratio level was in the normal range. Five patients (group N) had pretransplantation Gc-globulin values within the normal range (mean +/- 2 SD), and 12 patients had subnormal values (group S). In group N, mean Gc-globulin levels posttransplantation remained stable at a lower level than before transplantation but still within normal range. In this group, cold ischemia time correlated inversely with Gc-globulin levels on day 2 (r = -0.88; P <.05). In group S, normal mean levels were reached at a mean of 11 days after transplantation. However, almost half these patients had subnormal Gc-globulin levels at day 14. Complex ratio levels remained normal in the study period in both groups. Prothrombin index levels (plasma coagulation factors II, VII, and X) were identical in both groups and returned to normal 7 days posttransplantation, whereas plasma albumin levels were less than normal in both groups and further decreased after transplantation. In conclusion, the maintenance (group N) or reestablishment (group S) of serum Gc-globulin to normal levels occurred in the early posttransplantation course in the same time frame as the prothrombin index. Gc-globulin synthesis seems unrelated to albumin synthesis. A prolonged cold ischemia time may cause reduced Gc-globulin levels early after transplantation.

Etiology and outcome for 295 patients with acute liver failure in the United States.

Little information is available on acute liver failure (ALF) in the United States. We gathered demographic data retrospectively for a 2-year period from July 1994 to June 1996 on all cases of ALF from 13 hospitals (12 liver transplant centers). Data on the patients included age, hepatic coma grade on admission, presumed cause, transplantation, and outcome. Among 295 patients, 74 (25%) survived spontaneously, 121 (41%) underwent transplantation, and 99 (34%) died without undergoing transplantation. Ninety-two of 121 patients (76%) survived 1 year after transplantation. Acetaminophen overdose was the most frequent cause (60 patients; 20%), followed by cryptogenic/non A non B non C (NANBNC; 15%), idiosyncratic drug reactions (12%), hepatitis B (10%), and hepatitis A (7%). Spontaneous survival rates were highest for patients with acetaminophen overdose (57%) and hepatitis A (40%) and lowest for those with Wilson's disease (no survivors of 18 patients). The transplantation rate was highest for Wilson's disease (17 of 18 patients; 94%) and lowest for autoimmune hepatitis (29%) and acetaminophen overdose (12%). Age did not differ between survivors and nonsurvivors, perhaps reflecting a selection bias for patients transferred to liver transplant centers. Coma grade on admission was not a significant determinant of outcome, but showed a trend toward affecting both survival and transplantation rate. These findings on retrospectively studied patients from the United States differ from those previously gathered in the United Kingdom and France, highlighting the need for further study of trends in each country.

Serum Gc-globulin in the early course of multiple trauma.

OBJECTIVES: In patients with multiple trauma, actin released from damaged cells may cause severe circulatory disturbance due to thrombi formation. The aim of this study was to evaluate serum concentrations of the actin scavenger, Gc-globulin, in relation to the severity of injury and outcome. DESIGN: Prospective, longitudinal, observational study. SETTING: Trauma center at a university hospital. PATIENTS: Twelve patients with multiple trauma, consecutively included, according to defined criteria. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Serum Gc-globulin concentrations were measured at the time of admission and daily thereafter for 1 wk or until death. In all patients, the Gc-globulin concentration was significantly low (p < .0001), and the proportion of Gc-globulin bound to actin was already increased compared with normal values (p < .0001) by the time of hospital arrival. There was an inverse correlation between the mean concentration of serum Gc-globulin in the first week after trauma and the Injury Severity Score (r = -0.72, p < .05). Surviving patients had a significantly (p < .05) higher concentration of serum Gc-globulin in the first week after trauma compared with nonsurvivors. CONCLUSIONS: Serum concentrations of Gc-globulin were significantly low in trauma patients. The reduction took place within 60 mins after injury. Because the normal half-life of Gc-globulin is almost 48 hrs, our observations suggest a marked consumption of Gc-globulin immediately after the trauma. This finding could be the first clinical evidence that Gc-globulin plays a role in the systemic inflammatory response syndrome after trauma. This result is supported by the finding that lack of Gc-globulin was related to nonsurvival and the severity of the trauma.

Acetaminophen toxicity in an urban county hospital.

BACKGROUND: The prevalence and characteristics of acetaminophen-associated liver injury in hospitalized patients are not well defined. METHODS: We identified patients hospitalized for excessive acetaminophen ingestion at an urban county hospital over a 40-month period (1992 to 1995) and reviewed their medical records to determine the incidence and clinical features of the ingestions and their outcomes. RESULTS: Of the 71 patients studied, 50 were classified as having taken acetaminophen during suicide attempts and 21 as having accidentally poisoned themselves while attempting to relieve pain. The suicidal patients had ingested almost twice as much acetaminophen as those in the accidental-overdose group (median, 20 vs. 12 g; P=0.009). Among the patients for whom data were available, 63 percent of those in the accidental-overdose group and 25 percent of those in the suicidal group had chronic alcohol abuse (P=0.009). The patients in the accidental-overdose group more often had severe liver necrosis (aminotransferase levels, >3500 IU per liter; 52 percent vs. 14 percent; P=0.002), and were more likely to have hepatic coma (33 percent vs. 6 percent, P=0.006). There were four deaths (19 percent) in the accidental-overdose group and one (2 percent) in the suicidal group (P=0.04). Five patients -- three in the accidental-overdose group and two in the suicidal group -- had ingested 4 g of acetaminophen or less. Acetaminophen ingestion accounted for 12 percent of all patients hospitalized with overdoses (71 of 589) and 40 percent of patients with acute liver failure (10 of 25) during the study period. CONCLUSIONS: In an urban county hospital, patients hospitalized with acetaminophen toxicity related to accidental misuse had higher rates of morbidity and mortality than those who attempted suicide, even though the latter had taken more acetaminophen. A higher frequency of chronic alcohol abuse among the patients with accidental overdoses may be one explanation.

Reduced serum Gc-globulin concentrations in patients with fulminant hepatic failure: association with multiple organ failure.

OBJECTIVE: To evaluate the association between admission serum concentrations of the actin-scavenger, Gc-globulin, and the subsequent development of multiple organ failure in patients with fulminant hepatic failure. DESIGN: Retrospective study. SETTING: A hepatologic intensive care unit. PATIENTS: Seventy-nine patients with hepatic encephalopathy grade 3 or 4. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Serum admission concentrations of both total and nonactin-complexed (free) Gc-globulin were determined. The development of cardiovascular failure, renal failure, pulmonary failure, intracranial hypertension, and infections were recorded in each patient. Both total and free Gc-globulin values were significantly lower in the patients, compared with normal controls. The Gc-globulin values were significantly reduced in patients who subsequently developed cardiovascular failure (p < .01), intracranial hypertension (p < .001), and infections (p < .001), compared with those patients who did not. No differences were found between patients with and without pulmonary or renal failure. Patients with total Gc-globulin values in the lowest quintile had on average 2.6 organ failures, whereas patients with Gc-globulin concentrations in the highest quintile had 0.9 organ failures. The corresponding figures for the lowest and highest quintiles of free Gc-globulin were 3.0 and 1.1 organ failures, respectively. Both total and free Gc-globulin were inversely correlated to the number of organ failures (p < .005 in both cases). Patients with multiple organ failure (> or = 2 organ failures) had significantly reduced Gc-globulin values compared with patients without multiple organ failure (p < .0001). CONCLUSIONS: In patients with fulminant hepatic failure, the lowest admission Gc-globulin concentrations were associated with the subsequent development of cardiovascular failure, intracranial hypertension, and infections. Lack of Gc-globulin correlated significantly with the development of multiple organ failure and may be pathogenetically involved in this condition.

Haemodynamic changes after high-volume plasmapheresis in patients with chronic and acute liver failure.

OBJECTIVE: To evaluate the haemodynamic changes during treatment with high-volume plasmapheresis in patients with chronic liver failure compared to patients with acute liver failure. METHODS: Haemodynamic measurements were performed with a Swan-Ganz catheter and thermodilution technique. High-volume plasmapheresis (mean plasma exchange of 8.6 litres) was performed in 11 patients with chronic and 16 patients with acute liver failure. RESULTS: In patients with chronic liver failure, systemic vascular resistance index was unaltered: 1193 +/- 494 dynscm-5m2 before treatment versus 1180 +/- 399 dynscm-5m2 after. Mean arterial pressure increased from 69 +/- 11 mmHg to 78 +/- 13 mmHg (P < 0.05) and cardiac output increased from 8.1 +/- 2.4 l/min to 8.9 +/- 2.4 l/min (P < 0.05) during high-volume plasmapheresis. In patients with acute liver failure, systemic vascular resistance index increased from 1154 +/- 628 dynscm-5m2 to 1614 +/- 738 dynscm-5m2 (P < 0.001). In this group mean arterial pressure increased from 78 +/- 16 mmHg to 95 +/- 10 mmHg (P < 0.001) and cardiac output decreased from 9.6 +/- 3.7 l/min to 8.2 +/- 2.9 l/min (P < 0.01). CONCLUSION: The hyperkinetic circulation in chronic and acute patients was differently affected by high-volume plasmapheresis. We suggest that in chronic liver failure both portosystemic shunting and chronic peripheral vasodilation may contribute to the hyperkinetic syndrome, whereas in acute liver failure a humoral factor which can be removed by high-volume plasmapheresis is a main contributor.

Immunonephelometric quantification of group-specific component protein in patients with acute liver failure.

Serum levels of group-specific component (Gc) protein are useful in evaluating the likelihood of survival in patients with acute liver failure (ALF) who may be candidates for liver transplant surgery. Most methods for quantifying Gc protein concentration are either isotopic, manual, technically demanding, and/or time consuming to perform, and thus are not well suited for routine clinical use in a hospital setting. We modified and evaluated a recently described nonisotopic, fully automated, immunonephelometric method for quantifying serum Gc protein concentration and compared it to our previous immunoblotting method. In addition, we evaluated the effect of G-actin on the immunonephelometric measurement of Gc protein. Serum samples from 20 patients with ALF and from 20 age- and sex-matched clinic patients without liver disease were quantified by both immunoblotting and immunonephelometry. We assessed the intra-assay precision, correlation, and diagnostic accuracy of these methods in discriminating between individuals with no preexisting liver disease and those with ALF. Actin in 1.3- to 4-fold excess of Gc protein levels demonstrated minimal to no interference in the quantification of Gc protein by immunonephelometry. Immunonephelometry was more precise than immunoblotting. Gc protein values by immunonephelometry were similar to those obtained by immunoblotting, and the diagnostic accuracy of Gc protein concentration by immunonephelometry was similar to that observed by immunoblotting. Immunonephelometry provides a nonisotopic, fully automated, rapid, precise, accurate, and cost-effective method for quantifying serum levels of total Gc protein that is well suited for routine use in a hospital-based clinical laboratory.

[Gc-globulin in paracetamol poisoning]. / Gc-globulin ved paracetamolforgiftning.

Gc-globulin scavenges actin liberated from necrotic cells. We measured serum Gc-globulin and the degree of complexing with monomeric actin (complex ratio) in the initial phase of paracetamol (acetaminophen) intoxication and related this to the severity of liver necrosis and the clinical course. In eighteen patients with paracetamol intoxication serial measurements of serum Gc-globulin and complex ratio were determined from admission and every three hours thereafter. Eight patients developed hepatic encephalopathy (HE) and two of them died. On admission all patients had significantly reduced serum Gc-globulin levels compared to normal individuals, and patients with HE had significantly lower values than patients without HE. All patients with HE had at least three samples, where Gc-globulin was below 120 mg/l (35% of normal). Complex ratio on admission did not differ significantly in the patients with and those without HE. The peak complex ratio was higher in patients with HE than in patients without HE, and three of four patients with peak complex ratio above 75% had HE. In conclusion, Gc-globulin levels were found to be decreased in patients with paracetamol intoxication; this decrease correlated with the most severe sign of liver dysfunction, HE. Serum Gc-globulin below 120 mg/l and peak complex ratios above 75% may be critical values.

Admission levels of serum Gc-globulin: predictive value in fulminant hepatic failure.

Gc-globulin scavenges actin released from necrotic hepatocytes to the extracellular space. In 77 patients with fulminant hepatic failure (FHF) (excluding patients treated with liver transplantation), admission levels of serum Gc-globulin and degree of complexing with monomeric actin (complex ratio) were determined to evaluate their predictive values in relation to survival/nonsurvival. Gc-globulin levels were significantly reduced in 47 nonsurvivors, compared with 30 survivors (96 +/- 71 mg/L vs. 169 +/- 101 mg/L, P < .001), whereas the complex ratio in nonsurvivors did not differ significantly from that of survivors. Gc-globulin levels were significantly lower in 59 patients with non-acetaminophen-induced FHF, compared with 18 patients with acetaminophen-induced FHF (P < .01). Using a cutoff level of serum Gc-globulin of 100 mg/L, a lesser value correctly predicted nonsurvival in 79 percent of patients with non-acetaminophen-induced FHF, whereas a higher value predicted survival in 60 percent. In patients with acetaminophen-induced FHF, nonsurvival was correctly predicted in 100 percent of patients and survival in 53 percent. In comparison, the King's College Hospital (KCH) criteria correctly predicted nonsurvival and survival in 69 percent and 57 percent, respectively, of the same non-acetaminophen-induced FHF patients and in 60 percent and 38 percent, respectively, of the acetaminophen-induced FHF patients. Thus, in our study population, the predictive properties of Gc-globulin were in the same range as the KCH criteria. An advantage of Gc-globulin is that it gives an estimate of the outcome already on admission. Acute liver transplantation should be considered in FHF patients with Gc-globulin less than 100 mg/L.