Reliability of transient elastography for the diagnosis of advanced fibrosis in chronic hepatitis C.

BACKGROUND: Transient elastography (TE) has received increasing attention as a means to evaluate disease progression in patients with chronic liver disease. AIM: To assess the value of TE for predicting the stage of fibrosis. METHODS: Liver biopsy and TE were performed in 150 consecutive patients with chronic hepatitis C-related hepatitis (92 men and 58 women, age 50.6 (SD 12.5) years on the same day. Necro-inflammatory activity and the degree of steatosis at biopsy were also evaluated. RESULTS: The areas under the curve for the prediction of significant fibrosis (> or = F2), advanced fibrosis (> or = F3) or cirrhosis were 0.91, 0.99 and 0.98, respectively. Calculation of multilevel likelihood ratios showed that values of TE < 6 or > or = 12, < 9 or > or = 12, and < 12 or > or = 18, clearly indicated the absence or presence of significant fibrosis, advanced fibrosis, and cirrhosis, respectively. Intermediate values could not be reliably associated with the absence or presence of the target condition. The presence of inflammation significantly affected TE measurements in patients who did not have cirrhosis (p<0.0001), even after adjusting for the stage of fibrosis. Importantly, TE measurements were not influenced by the degree of steatosis. CONCLUSIONS: TE is more suitable for the identification of patients with advanced fibrosis than of those with cirrhosis or significant fibrosis. In patients in whom likelihood ratios are not optimal and do not provide a reliable indication of the disease stage, liver biopsy should be considered when clinically indicated. Necro-inflammatory activity, but not steatosis, strongly and independently influences TE measurement in patients who do not have cirrhosis.

Interferon and thymosin combination therapy in naive patients with chronic hepatitis C: preliminary results.

AIMS/BACKGROUND: This randomized study was performed to compare the efficacy of interferon-alpha (IFN-alpha) + thymosin alpha 1 (Talpha1) treatment to that of IFN-alpha alone in light of biochemical and virological response of naive patients with chronic hepatitis C. METHODS: Seventeen patients were treated with IFN alpha-2b (3 million units MU three times a week) + Talpha1 (1 mg twice weekly); the other 17 patients received only IFN alpha-2b at the same dose. All patients were treated for 6 months and followed up for 12 months. Biochemical (ALT values) and virological (HCV-RNA) responses to treatment were determined. RESULTS: Combination therapy showed significantly higher efficacy than monotherapy in achieving biochemical and virologic end-of-treatment response (p<0.05). At 12 month follow-up, the sustained biochemical response was slightly greater in patients treated with combination therapy than in those treated with monotherapy. No significant difference in response by HCV-1b subtype was observed between the two treatment groups; however, HCV-2c subtype showed a trend to responding better to IFN-alpha+Talpha1 than to IFN-alpha alone. CONCLUSIONS: These data suggest that the immune modulator Talpha1 may be additive or synergistic with IFN-alpha in normalizing end-treatment biochemical and virological responses in patients with chronic hepatitis C. Higher doses and/or more prolonged courses may improve the sustained response rates to this treatment.

A pilot study on the liver protective effect of silybin-phosphatidylcholine complex (IdB1016) in chronic active hepatitis.

In order to assess the liver protective activity and the antioxidant properties of a new silybin complex (IdB1016), we carried out a short-term pilot study on 20 patients with chronic active hepatitis (CAH), randomly assigned to 240 mg of silybin b.i.d. (10 patients, 4 m/6 f, mean age: 50 years) or placebo (10 patients, 2 m/8 f, mean age: 55 years). Blood samples were collected before and after 7 days of treatment for liver function tests (LFTs), malonaldehyde (MDA) as an index of lipid peroxidation, and copper (Cu) and zinc (Zn), two trace elements involved in protecting cells against free radical-mediated lipid peroxidation. In the treated group, there was a statistically significant reduction of mean (+/- SEM) serum concentrations of aspartate aminotransferase (AST) from 88.0 (+/- 13.3) to 65.9 (+/- 7.5) u/l, (p < 0.01), of alanine aminotransferase (ALT) from 115.9 (+/- 12.9) to 82.5 (+/- 10.6) u/l (p < 0.01), of gamma-glutamyltranspeptidase (gamma-GT) from 51.4 (+/- 9.3) to 41.3 (+/- 4.2) u/l (p < 0.02) and of total bilirubin (TB) from 0.76 (+/- 0.08) to 0.53 (+/- 0.04) mg/dl (p < 0.05). Alkaline phosphatase (AP) fell slightly from 143.4 (+/- 6.4) to 137.5 (+/- 7.8) u/l. There were no significant changes in MDA, Cu or Zn serum concentrations. These results show that IdB1016 may improve LFTs related to hepatocellular necrosis and/or increases membrane permeability in patients affected by CAH.

[Ursodeoxycholic hemisuccinate in the treatment of chronic active hepatitis. A controlled clinico-therapeutic study]. / L'emisuccinato dell'acido ursodesossicolico nel trattamento dell'epatite cronica attiva. Studio clinico-terapeutico controllato.

This controlled study was performed on 36 patients affected by HBV and/or HCV correlated chronic hepatitis (CAH). Eighteen of them received 300 mg of UDCA-hemisuccinate orally twice a day for six months; the other 18 received 200 mg of S-adenosyl-methionine (SAMe) twice a day for six months. The two groups were determined randomly. Treatment with UDCA-hemi-succinate produced a statistically significant reduction in ALT (from 167 +/- 17 to 119 +/- 15 U/l; p < 0.0001), AST (from 122 +/- 14 to 86 +/- 11 U/l; p < 0.0001) and y-GT (from 81 +/- 10 to 53 +/- 6 U/l, p < 0.0001). The results obtained suggest that UDCA-hemi-succinate may be useful in the long-term treatment of chronic liver diseases of viral aetiology because it improves the biochemical parameters of hepatocellular necrosis and/or increased liver cell permeability.

Hepatic lipid peroxidation and aldehyde dehydrogenase activity in alcoholic and non alcoholic liver disease.

It has been suggested that lipid peroxidation plays a role in the pathogenesis of chronic alcoholic liver disease (CALD). However, whether or not CALD differs from chronic non alcoholic liver disease (CLD) in lipid peroxidation, is still questionable. Thirty-eight patients affected by CALD and CLD who were matched for age, sex, nutrition and liver function tests (LFTs) and 17 controls (C) took part in this study. The following tests were performed: serum and liver malondialdehyde (MDA) determination by the TBA test, liver total glutathione (GSH) estimate, mitochondrial (ALDH2) and cytosolic (ALDH1) aldehyde dehydrogenase activity determinations. Patients who showed signs of malnutrition were excluded from this study. Serum and hepatic TBA-reactive substances resulted in a slight increase in chronic liver patients compared to controls but did not show any difference between CALD and CLD groups. Liver total glutathione did not show any change. Hepatic ALDH2 activity was significantly (P less than 0.01) higher in CALD than in CLD and control patients whereas ALDH1 did not show any difference. These results suggest that the increased lipid peroxidation in CALD and in CLD is probably secondary to liver damage rather than being the pathogenic factor.

Expired hydrocarbons in patients with chronic liver disease.

Fifty patients with various types of liver disease and twenty-one healthy subjects were examined for lipoperoxidation in vivo by gaschromatographic assay of volatile hydrocarbons (ethane, ethylene, propane, n-butane, n-pentane) in breath gases. In 15 patients with alcoholic cirrhosis the amount of expired pentane was greater than in all the other groups examined. No significant increase of exhaled ethane, in contrast, was detected in the same patients. These results seem to indicate that pentane is a more sensitive index than ethane for ethanol-induced lipoperoxidation. This simple and non-invasive method opens up promising new opportunities for clarifying in humans, the role of lipoperoxidation in ethanol-induced liver damage, as well as in other chronic liver disease.

Effect of alcoholic cirrhosis on ethane and pentane levels in breath.

Lipid peroxidation can be monitored by measuring one or several highly volatile alkanes in exhaled air. The concentrations of ethane and pentane were determined in breath samples from patients with alcoholic and non-alcoholic cirrhosis as well as from healthy subjects. The greatest increase of exhaled pentane was found in 17 patients with alcoholic cirrhosis (2.85 +/- 2.37 pmol/ml) in comparison with 10 patients with non-alcoholic cirrhosis (0.71 +/- 0.33 pmol/ml) and 10 control subjects (0.59 +/- 0.41 pmol/ml). On the contrary, no significant difference was detected as far as exhaled ethane is concerned. These data suggest that: a) gas-chromatographic determination of exhaled pentane may play a significant role in detecting alcohol-induced liver disease; b) hepatic injury may be mediated by lipid peroxidation in these patients.

[Quick's time and derived times in the study of the extrinsic course of the coagulation process. The PIVKA (protein induced by vitamin K absence or antagonists) in states of chronic disseminated intravascular coagulation]. / Il tempo di quick e tempi derivati nello studio della via estrinseca del processo coagulativo. i PIVKA (protein induced by vitamin k absence or antagonists) in condizioni di coagulazione intravascolare disseminata cronica

After reviewing the available methods for the clinical study of the extrinsec way of the coagulative process (Quick's time, Owren's Thrombotest and Normotest), the AA. explain what is the significance that the most of hte researchers ascribe to time-value discrepancies between Thrombotest and Normotest. The AA. remember that while the former is sensitive to the presence of certain inhibitors called PIVKA (Protein Induced by Vitamin K Absence or Antagonists), just as Quick's original time; the latter is on the contrary insensitive to them. Then it provides more significant data about the real rate of factors II, VII, and X. Such inhibitors have been found also in subjects that did not undergo any anti-vitamin K therapy and peculiarly in cases in which a Intravascular Coagulation occurred. Therefore the AA. thought to verify the hypothesis that the detection of a discrepancy between TT and NT could be useful in the clinical diagnosis of I.C. which is a serious and often hardly detectable disorder of haemostasis. The AA. have therefore tested 72 patients, 65 of which showed the evidence of I.C. and 7 with I.C. probabilities. The discrepancy values that were obtained are showed in Table I. The first group (65 cases) was furtherly divided into four subgroups, according to the positivities obtained from SDPS test, as shown in Table II. The AA. can therefore come to the following conclusions: a) In human Intravascular Coagulation, the discrepancy between NT/TT may occur with a frequency of 57 per cent but it is not a constant event. b) The discrepancy rate is generally of low degree, being of high degree only in twelve cases (18.5 per cent. c) Analyzing the discrepancy presence and rate in relation to the number of SDPS test positivities, we can notice that the values are remarkably scattered and it is not possible, only on the basis of these data to make a statistical evaluation of their significativity because the groups are not comparable among them, being in exc3ss the cases in which paracoagulation occurs in a low degree. We can only state that the absence of discrepancy predominates in the cases in which a low number of positivities of SDPS test occurs, and on the contrary the discrepancy is a constant event in the cases in which SDPS test shows a large number of positivities. In consitive test to detect Intravascular Coagulation, but we think the positivity of this test may be a support in doubtful cases.