[Clinico-statistical considerations on the incidence of myocardial infarct in aged heart patients].
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Coronary Disease↗
Biomedical subjects
E Giannini
Publications and source records attributed to E Giannini.
Cholestasis is the main determinant of abnormal CA 19-9 levels in patients with liver cirrhosis.
BACKGROUND/AIMS: Altered CA19-9 levels are commonly found in patients with liver cirrhosis though a clear explanation for this finding has not yet been given. The aim of this study was to investigate whether CA19-9 levels might be related to alterations in biochemical parameters and/or to functional impairment in cirrhotic patients with and without hepatocellular carcinoma. METHODS: We studied 126 patients with liver cirrhosis, 60 of whom also had hepatocellular carcinoma. CA19-9 values were related to clinical, biochemical and functional parameters. In half of the patients CA19-9 levels were related to the monoethylglycinexylidide test, which is a dynamic liver function test. RESULTS: In more than half the cases CA19-9 values were above the upper limit. Liver function worsening as assessed by Child-Pugh's score and monoethylglycinexylidide test did not seem to influence the alteration of the marker. By contrast, in univariate analysis CA19-9 correlated with aminotransferases, gamma-glutamyltransferase and alkaline phosphatase. Multivariate analysis showed that besides alkaline phosphatase also the presence of hepatocellular carcinoma might influence the alteration of CA19-9, although the marker was of no use for the diagnosis of liver cancer in patients with altered though not diagnostic alpha-fetoprotein levels. CONCLUSIONS: In our study we confirmed the correlation of CA19-9 levels with cholestasis and cytolysis parameters. Moreover, we found no association between CA19-9 levels and impaired liver function as assessed by means of the Child-Pugh's score and the monoethylglycinexylidide test, which is cholestasis-independent and explores liver metabolic and clearance activities. The cholestatic picture that characterizes liver cirrhosis might enhance the expression and passage of the marker from the bile to the blood. The addition of CA19-9 assessment is not useful for the diagnosis of hepatocellular carcinoma in patients with non-diagnostic levels of alpha-fetoprotein. Caution should therefore be used when evaluating CA19-9 in cirrhotic patients with cholestasis, since false positive results may occur.
Adult↗
Probability of non-response during interferon therapy in patients with chronic hepatitis C.
BACKGROUND/AIMS: About 50% of patients with chronic hepatitis C do not respond to interferon therapy and this failure is expensive. The aim of this study was to identify possible predictive factors of biochemical non-response during interferon therapy among biochemical, virological (HCV genotype), histological (Knodell's score) and pharmacokinetic (monoethylglycinexylidide formation test) pre-treatment parameters. METHODOLOGY: Our study included 60 patients with chronic hepatitis C undergoing a course of Interferon therapy. Patients whose serum ALT levels were normal at the 3rd month of therapy and remained so until the end of treatment were regarded as responders. RESULTS: In univariate analysis, only the gamma-glutamyltransferase (gamma-GT) and the gamma-GT/alanine aminotranferase ratio were significantly higher in non-responder patients. Multivariate logistic analysis showed that high gamma-GT levels, high histological activity index, low monoethylglycinexylidide formation rate and viral genotype 1 were the best combination for the identification of non-responder patients (16.7% error rate). By adding alanine aminotranferase modification at the 1st month of therapy the probability error was reduced to 5%. CONCLUSIONS: These results show that the combination of biochemical, histological, virological and pharmacokinetic pre-treatment variables, associated with alanine aminotranferase modification at the 1st month of therapy, can predict non-response to interferon and allow therapeutic modifications.
Adult↗
Leptin levels in nonalcoholic steatohepatitis and chronic hepatitis C.
BACKGROUND/AIMS: Leptin is a peptide which regulates food intake and energy expenditure. Moreover, it is involved in the homeostasis of body composition and is linked to the regulation of insulin signaling, thus playing an important role in liver fat storage. Steatosis is a common finding in chronic hepatitis C, and both viral and metabolic factors have been suggested to explain the presence of this histological characteristic. In order to study leptin in chronic liver disease characterized by the presence of steatosis, we evaluated its serum levels in patients with nonalcoholic steatohepatitis (NASH), in chronic hepatitis C (CHC) patients with no histological findings of steatosis, and CHC patients with steatosis but no risk factors for its development. METHODOLOGY: We studied 6 male patients with NASH whose diagnosis was made on the basis of histological findings and clinical criteria. From among a cohort of 170 CHC patients we put together 2 groups of 6 male patients each (with or without steatosis at liver biopsy examination), who had no risk factors for NASH. Male patients were chosen in order to avoid gender influence on leptin levels. Further criteria for admission were similar impairment of liver metabolic function as assessed by the monoethylglycinexylidide (MEGX) test and, in patients with CHC, similar body mass index (BMI) and histological staging. Moreover, we evaluated leptin/BMI ratio, in order to rule out BMI influence on leptin levels. Leptin levels were assessed by means of radioimmunoassay. RESULTS: We found that BMI was higher in NASH compared to CHC (27.2 +/- 2.9 vs. 23.9 +/- 1.8; p = 0.01). Analysis of serum leptin levels showed an increasing trend starting from patients with CHC without steatosis (3.2 +/- 0.4 ng/ml), through CHC patients with steatosis (4.2 +/- 0.7 ng/ml) up to patients with NASH (5.7 +/- 2 ng/ml), although the differences observed were not statistically significant. Moreover, the ratio of leptin to BMI also followed the same trend showing increasing values (CHC without steatosis = 0.04 +/- 0.02; CHC patients with steatosis = 0.17 +/- 0.03; NASH = 0.203 +/- 0.07). Leptin levels and BMI showed a significant relationship (n = 18; r = 0.60; p < 0.01). CONCLUSIONS: The increasing trend observed in leptin serum levels among the different groups of patients showed that in chronic liver disease characterized by the presence of steatosis, leptin signaling is preserved. Moreover, CHC factors different from the metabolic ones should be investigated in order to explain the presence of steatosis. Further studies on broader groups of patients are needed to verify these preliminary results.
Adult↗
13CO2 excretion in breath of normal subjects and cirrhotic patients after 13C-aminopyrine oral load. Comparison with MEGX test in functional differentiation between chronic hepatitis and liver cirrhosis.
BACKGROUND/AIMS: Liver function can be evaluated using 13C breath tests that explore liver Cytochrome P450 activity. Aminopyrine is one of the first compounds used in liver function testing. Lidocaine metabolism to monoethylglycinexylidide is also a valid tool to assess liver function. Although liver Cytochrome P450 metabolizes both compounds, lidocaine metabolism is flow-dependent while aminopyrine metabolism does not depend on liver blood flow. METHODOLOGY: The 1st part of the study evaluated the appearance and disappearance rate of 13CO2 in the breath of both normal subjects and in cirrhotic patients, so as to establish optimal sampling times and to evaluate the amount of time needed before performing a subsequent breath test. The 2nd part of the study compared the aminopyrine breath test with the monoethylglycinexylidide test in patients with chronic hepatitis or cirrhosis. RESULTS: Complete 13CO2 disappearance was recorded 24 hours after the test in normal subjects, while it took 3 days to disappear from the breath of cirrhotic patients. Breath sampling at 60, 120 and 180 min were equally valid in differentiating chronic hepatitis from cirrhosis. The aminopyrine breath test and monoethylglycinexylidide test showed a good yet not close correlation. CONCLUSIONS: This study showed that in cirrhotic patients a 13C breath test can be performed 3 days after the previous one. In chronic hepatitis and cirrhotic patients, the aminopyrine breath test and the monoethylglycinexylidide test evaluated similar, but not identical, hepatic subfunctions, suggesting that multiple 13C breath test using different substrates could explore liver function better.
Adult↗
Tauroursodeoxycholic acid administration as adjuvant therapy in cirrhotic patients on transplantation waiting lists.
BACKGROUND/AIMS: The lack of organ availability and an increased number of end-stage cirrhotic patients has led to the lengthening of liver transplantation waiting lists. The progressive worsening of clinical and functional performance in patients awaiting the graft is one of the factors implicated in the increased mortality during the wait and in poor transplantation outcome. In this work our aim was to evaluate the effects of tauroursodeoxycholic acid administration on biochemical, clinical and functional parameters in a group of cirrhotic patients consecutively placed onto our liver transplantation waiting list. METHODOLOGY: Ten cirrhotic patients underwent biochemical, clinical and functional evaluation at the time of entering on our liver transplantation waiting list, then tauroursodeoxycholic acid was administered until liver transplantation. Complete evaluation was repeated every 2 months. The results were compared to those of a comparable historical control group that had undergone liver transplantation the year before the study. RESULTS: All patients were transplanted within 6 months from insertion on the waiting list. Longitudinal analysis of the treated group showed that cholestasis and cytolisis parameters constantly decreased and that gamma-glutamyl transpeptidase was significantly lower compared to baseline values at the 4th month of therapy. Clinical and functional parameters remained stable during follow-up. Comparison with the control group showed that gamma-glutamyl transpeptidase, alkaline phosphatase and both aminotransferases were reduced at the 4th month of therapy. Fewer days of hospital stay and less intensive care were required in the treated group. CONCLUSIONS: Treatment of end-stage cirrhotic patients awaiting liver transplantation with tauroursodeoxycholic acid improves biochemical parameters of cytolisis and cholestasis, and furthermore helps to maintain clinical and functional stability during the wait. Improved biochemical conditions and steady clinical-functional performance may promote better short-term transplant outcome.
Case-Control Studies↗
Does surveillance for hepatocellular carcinoma in HCV cirrhotic patients improve treatment outcome mainly due to better clinical status at diagnosis?
BACKGROUND/AIMS: Cirrhotic patients with hepatitis C virus infection are a group at higher risk for hepatocellular carcinoma. Conventional screening programs detect only few early hepatocellular carcinomas that are eligible for radical treatment. Our aim was to compare characteristics of patients, modality of treatment, and outcome in anti-HCV positive cirrhotics with hepatocellular carcinoma diagnosed during follow-up, or incidentally. METHODOLOGY: Sixty-one hepatocellular carcinomas were consecutively diagnosed in cirrhotic anti-HCV patients from 1993-1998 among which 34 during biannual ultrasonographic-biochemical follow-up and the others incidentally. Child-Pugh's score, alpha-fetoprotein levels, uni- or multifocality of the tumor, and treatment and survival of the patients were then analyzed on the basis of modality of diagnosis. RESULTS: Surgical treatment was feasible only in a minority of patients. Radical and palliative treatment was more frequent among patients with HCC diagnosed during follow-up. Child-Pugh's score was lower in these patients, moreover their survival rate was better. Analysis of survival of patients treated with the same procedure and grouped by modality of diagnosis did not demonstrate any differences. Regression analysis showed that patients with a lower Child-Pugh's score, one nodule, with a tumor diagnosed during follow-up and who were treated had a better survival rate. CONCLUSIONS: In our population surveillance did not detect a higher percentage of curable HCC. Nevertheless the results of palliative treatment and of curative treatment overlapped. Overall better outcome was observed in patients with preserved liver function whatever the treatment. Surveillance allowed us to diagnose HCC in patients with these characteristics thus leading to an improved survival rate.
Aged↗
A new assay for hepatitis C virus (HCV) core antigen detection: an alternative to nucleic acid technologies in positive or indeterminate anti-HCV subjects?
Markers of viral replication are fundamental tools for understanding the mode of transmission, diagnosis and management of hepatitis C virus (HCV) infection. A new enzyme-linked immunosorbent assay for quantitative detection of free and complexed HCV core antigen (HCV Ag) has been developed. The aim of this study is to evaluate the clinical performance of the new test and compare it with the most widely used commercially available RT-PCR-based assay. To determine the cut-off value we tested 60 samples from anti-HCV negative samples and selected a qualitative cut-off value of 3 pg/ml. To evaluate the usefulness of the new assay in confirming serologically indeterminate results we collected 62 sera. To evaluate the HCV Ag and HCV-RNA relationship we tested 245 samples from patients with different clinical conditions. The results of 61 out of 62 (98.4%) anti-HCV indeterminate samples were found to agree, whereas only one serum was found to be RT-PCR positive and HCV Ag negative. We also found the results to agree in 77.6% (190/245) of the samples from infected patients, while we observed higher agreement in untreated patients, both with and without evidence of liver damage. The correlation coefficient (r) observed between HCV Ag and HCV-RNA was 0.88. The regression line meets the cut-off value at an HCV-RNA concentration of approximately 40,000 IU/ml. In conclusion, we found that the results from the total HCV Ag test agree with the RT-PCR results and therefore we believe that this test could become a useful tool for the diagnosis and management of HCV infection.
Hepatitis C Antigens↗
[Studies on populations of the planarian Dugesia benazzii with two types of oocytes: statistical analysis of the relative frequencies and observations of a genetic order].
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Analysis of Variance↗
[The behavior of liver function in diabetes mellitus and its complications].
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Diabetes Mellitus↗
Lidocaine elimination and monoethylglycinexylidide formation in patients with chronic hepatitis or cirrhosis.
BACKGROUND/AIMS: The aim of this study was to evaluate the relationship between plasma elimination of lidocaine and monoethylglycinexylidide (MEGX) formation, which is considered to be a quantitative liver function test. METHODOLOGY: The study included ten healthy subjects and 54 patients: 27 with chronic hepatitis and 27 with cirrhosis. Lidocaine and MEGX were measured at 0, 2, 5, 10, 15, 30 min and then every 30 min for 180 min using the TDX system. RESULTS: In cirrhotic patients, the lidocaine half-life of the slow decline phase of the plasma disappearance curve (beta-HL) and the lidocaine half-life of hepatic elimination from the second compartment (K20-HL) proved to be significantly abnormal, as did all parameters of MEGX formation. In chronic hepatitis, both the lidocaine kinetics and the MEGX formation parameters were within the normal range. In chronic hepatitis patients, MEGX formation (AUC 0-180) was significantly correlated to K20-HL (rs = -0.633, p < 0.001) and to the rapid decline phase of the plasma disappearance curve (alpha-HL, rs = -0.483, p < 0.05). In cirrhotic patients, MEGX was significantly correlated to K20-HL (rs = -0.423, p < 0.05) and to beta-HL (rs = -0.500, p < 0.01). CONCLUSIONS: These results show that in chronic active hepatitis, MEGX formation from lidocaine is maintained as a metabolic process, whereas it is altered in cirrhotic patients. The interrelationship between lidocaine elimination and MEGX formation were somewhat different in the two liver diseases.
Adolescent↗