A study about mechanisms of des-gamma-carboxy prothrombin's production in hepatocellular carcinoma.

AIM: Des-gamma-carboxy prothrombin (DCP) is an abnormal prothrombin, increased in serum of patients with hepatocellular carcinoma (HCC) as result of an acquired defect of post-translational carboxylation of prothrombin's precursor. It is unclear if the reduced activity of gamma-carboxylase is secondary to vitamin K deficiency or to an altered gene encoding this enzyme. The aim of this study was to evaluate the effect of vitamin K administration on DCP and alpha-fetoprotein (AFP) levels, to identify a relationship between vitamin K and DCP serum levels and to investigate mechanisms of serum elevation of DCP levels. METHODS: The authors determined DCP and AFP serum levels and vitamin K concentration in 64 cirrhotics with HCC and in 60 cirrhotic subjects without HCC. In HCC subjects DCP and AFP levels were measured before and after vitamin K administration. A t-test for unpaired data was applied (P values <0.05 statistically significant). RESULTS: Only HCC patients had detectable levels of DCP and significant AFP levels. Administration of vitamin K reduced DCP but not AFP levels in HCC patients. No correlation was observed between vitamin K concentration and DCP levels: vitamin K concentration was similar both in HCC patients and in control group without HCC; HCC patients had the same vitamin K concentration regardless of elevated o reduced DCP levels after vitamin K administration. CONCLUSION: DCP detectable serum levels are the result not only of vitamin K deficiency or selective defects of carboxylase, because probably alterations of membrane receptors or cytoplasmatic transfers, that are necessary for the function of vitamin K, are involved.

The HFE gene heterozygosis H63D: a cofactor for liver damage in patients with steatohepatitis? Epidemiological and clinical considerations.

BACKGROUND: The altered status of iron metabolism is reported in hereditary haemochromatosis and in non-alcoholic liver fatty disease. We investigated the relation between the H63D HFE mutation gene and non-alcoholic steatohepatitis (NASH). METHODS: We studied as outpatients, 272 Italian persons with NASH and compared them with 430 healthy subjects. Genetic screening for haemochromatosis, haematochemical tests, liver ultrasound examination and liver biopsies were carried out. RESULTS: The prevalence of heterozygosity for the H63D mutation in NASH patients was not significantly greater than controls. In assessing the C282Y HFE gene mutation alone, the percentage of heterozygosis for C282Y was not different in subjects with NASH compared with controls. As regards a mutation C282Y/H63D there was no significant difference between the two groups. The mean fibrosis score was not significantly different between subjects of group A, with and without HFE mutations (1 +/- 8 and 1 +/- 9, respectively); we did not find a significant correlation between hepatic iron concentration and histological score between subjects. CONCLUSION: We have not found a significantly increased prevalence of the mutation H63D in the HFE gene in our patients with NASH. In these patients there was no more severe hepatic histological score when compared with NASH subjects without HFE mutations.

[HAV infection in patients with chronic hepatitis C]. / Infezione da HAV in pazienti con epatite cronica HCV-correlata.

AIM: In most cases, hepatitis A virus (HAV) infection causes a self-limiting benign acute hepatitis which confers permanent acquired immunity. However, in patients with pre-existing chronic hepatitis, HAV superinfection can cause acute hepatitis with severe progression leading to a fulminant form or linked to the risk of a rapid deterioration of hepatic function. For such a reason, some Authors recommend anti-HAV vaccination for subjects with HCV-correlated chronic hepatitis before the initiation of peg-Interferon and Ribavirin treatment. Subsequently, the real prevalence of IgG anti-HAV antibodies in patients with HC HCV-related and in healthy subjects from Eastern Sicily has been verified. PATIENTS AND METHODS: In 254 subjects affected by HC HCV-related it has been carried out the research of antibodies IgG and IgM anti HAV. The control group was formed by 685 non hepatopathic subjects, subdivided in range of ages. RESULTS: 97.64% out of the patients affected by HC HCV related exhibit antibodies IgG anti HAV, while only 2.36% of them was negative. The prevalence of infection in the control group has been stratified in relation to different ranges of age of the people taken into consideration. CONCLUSIONS: The results obtained in this study performed in our geographical area, let us to suggest that it is not necessary the anti HAV vaccination during the phase of pre-treatment for HC HCV-related.

Role of Helicobacter pylori in patients with portal hypertensive gastropathy by liver cirrhosis hepatitis C virus-related.

AIM: Portal hypertensive gastropathy (PHG) defines a pathological endoscopic picture characterized by the presence of alterations of the gastric mucosa found in patients with hepatopathy associated to an initial or evident portal hypertension. Gastropathy appears with two forms of different seriousness: the mild form, characterized by diffused congestion, petechiae of gastric mucosa (scarlatina type rash) and by the presence of typical hyperemic and edematous polygonal areas, delimited by a thin snake skin reticulation. In the severe form, together with such aspects, mucosal erosion, red spots, or a diffused hemorrhagic gastropathy are added. The pre-eminent pathogenetic element of such lesions seems to be the pathological increase of the portal pressure. The role of the Helicobacter pylori (H. pylori) in the development of these alterations, in terms of prevalence of infection in hepatopathic subjects, is still controversial. The authors have performed a research to verify if the H. pylori infection is correlated to the presence and/or to the gravity of PHG. METHODS: One-hundred and nine patients, all suffering from hepatitis C virus (HCV)-correlated liver cirrhosis, with clinical and/or instrumental signs of portal hypertension have been analysed. RESULTS: The histological prevalence of the infection from H. pylori in our statistical analysis was of 23.8% (26/109 patients). CONCLUSIONS: The H. pylori infection appears to be not significant for the determination and the preservation of PHG.

The combined endoscopic therapy (band ligation and sclerosis) in the eradication of the esophageal varices in the cirrhotic patient: our experience.

AIM: In course of liver cirrhosis, esophageal varices develop with an incidence of 8-15% a year, and they constitute a sign of seriousness of portal hypertension. The risk of bleeding is estimated around 10-15% a year. The varices hemorrhage causes a high rate of mortality (around 30-35% for every hemorrhagic event). It follows that it is necessary to plan prophylactic strategies for all the cirrhotic patients, who are at risk of bleeding, or have already bled. Medical treatment with beta-blockers is indicated in the prophylaxis of the first bleeding, while endoscopic treatment represents now the most effective methodology either in acute bleeding, or in the prophylaxis of hemorrhage relapses. The available endoscopic methodologies are the sclerosis or band ligation of esophageal varices. However, unanimous consent about the greater effectiveness of a methodology compared to the other one doesn't exist. As far as the varices eradication is concerned, the authors have done a research to verify if the combined techniques, proposed in various studies appeared in literature, can have some advantages, in comparison with the single methodologies. METHODS: Thirty-seven patients have been treated: 27 only with sclerosis and 10 with combined methodology (band-ligation followed by sclerosis of the small residual varices). RESULTS: The group treated with the combined therapy have shown a reduction in relapses and in the main side effects and a better patients' compliance. CONCLUSIONS: The combination of the two methodologies can have some advantages as for security, easiness of execution, reduction in complications, in varices relapse and, therefore, in the hemorrhagic relapses.

Randomized clinical trial to compare the effects of methadone and buprenorphine on the immune system in drug abusers.

RATIONALE: Buprenorphine may be a useful alternative option to methadone in addicts. Opioids can produce severe changes in the immune system. OBJECTIVES: The objectives of this study are to compare the effect of sublingual buprenorphine and methadone on the immune system and to compare the two substances on the drying-out program compliance. METHODS: We studied 62 randomized outpatients for a period of 12 months. Subjects (55 males and 7 females; mean age 25+/-4 years; average history of heroin abuse being 2 years) on maintenance treatment were assigned in two groups (A and B). Methadone chloride (medium dose 100 mg/day) was administered to group A, whereas group B received sublingual buprenorphine (32.40+/-2.8 mg/day). Urine toxicological screening, plasma levels of TNF-alpha interleukin-1, interleukin-beta, lymphocyte CD14 and a self-rating depression questionnaire were measured. RESULTS: Urine screening was negative for opiates in 17.6% of group A and in 10.7% of group B (p<0.001; r = 0.62). Depression score was 62+/-2 in group A and 55+/-3 in group B (p < 0.01). Cytokine and CD14 revealed higher concentrations both in groups A and B without significant differences (p > 0.05) between the two groups. CONCLUSIONS: The effects of buprenorphine and methadone tested on the immune system were overlapping in our patients. The elevated cytokine levels observed may suggest that the two drugs stimulate immunologic hyperactivation of an immune system that was formerly inhibited by heroin. Furthermore, our data suggest that buprenorphine can be a valid alternative to methadone in maintenance treatment of chronic heroin abuse and referred a marked decline in depression.