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R Testa

Publications and source records attributed to R Testa.

At least 19 recordsLinked to original sources

Trans-catheter arterial chemoembolisation for hepatocellular carcinoma in patients with viral cirrhosis: role of combined staging systems, Cancer Liver Italian Program (CLIP) and Model for End-stage Liver Disease (MELD), in predicting outcome after treatment.

BACKGROUND: Trans-catheter arterial chemoembolisation (TACE) is the most common palliative treatment for hepatocellular carcinoma (HCC). The therapeutic options depend both on the characteristics of the tumour and on functional staging of the cirrhosis. AIM: To evaluate the effects of TACE on the survival of cirrhotic patients with HCC according to different staging systems [Okuda score, Cancer Liver Italian Program (CLIP) score, Model for End-stage Liver Disease (MELD) score] and in relation to the side-effects of TACE. METHODS: Fifty cirrhotic patients, 36 CTP class A and 14 class B, underwent 106 TACE treatments with mitoxantrone. Survival at 12, 24, and 36 months was evaluated. RESULTS: MELD at 12 months and CLIP at 24 months were identified as significant variables associated with survival. Combined cut-offs of CLIP and of MELD identified four subgroups of patients with different survivals, at 12, 24 and 36 months, respectively: CLIP >or= 2 and MELD >or= 10 (63%, 20% and 0%), CLIP < 2 and MELD >or= 10 (73%, 40% and 22%), CLIP >or= 2 and MELD < 10 (73%, 40% and 22%) and CLIP < 2 and MELD < 10 (100%, 63% and 50%). Post-TACE side-effects proved to have no influence on survival. CONCLUSION: In patients with poor probability of survival (CLIP >or= 2 and MELD >or= 10), TACE must be planned with a great deal of caution, while in patients with possibly good outcomes (CLIP < 2 and MELD < 10), more 'aggressive' therapy should be taken into consideration.

Adult↗

Apolipoprotein E polymorphisms and mortality in Italian type 2 diabetic patients.

AIMS: To determine if apolipoprotein E polymorphism is associated with cardiovascular or all-cause mortality in Italian Type 2 diabetic patients. METHODS: A prospective study of mortality in Type 2 diabetic patients (n = 433) as a function of apolipoprotein E phenotype, which was assessed at entry into the study. During follow up (10 years), 110 (25.4%) patients died of which 66 (15.2%) were the result of cardiovascular causes. Cause of death was established from death certificates and clinical records. The clinical status of the survivors was determined at the end of the study. RESULTS: Apolipoprotein E polymorphisms were not associated with excess cardiovascular or all-cause mortality in the Italian Type 2 diabetic patients either in univariate or multivariate analyses. Age, duration of diabetes and glycated haemoglobin levels at entry were the primary determinants of premature mortality in the diabetic population. CONCLUSIONS: Apolipoprotein E polymorphisms are not markers for premature mortality in Italian Type 2 diabetic patients. The impact of apolipoprotein E mutations may be attenuated by environmental factors, notably a healthier diet, in Italian patients.

Apolipoproteins E↗

Effects of intravenous and infravesical administration of suramin, terazosin and BMY 7378 on bladder instability in conscious rats with bladder outlet obstruction.

OBJECTIVE: To evaluate the effect of the nonselective purinergic antagonist suramin and the alpha1-adrenergic antagonists, terazosin and BMY 7378, given intravenously or infused directly into the bladder during cystometry in conscious rats with bladder outlet obstruction induced by urethral ligation. MATERIALS AND METHODS: Cystometry was performed in conscious female rats recording bladder volume capacity (BVC), evaluated as the amount of saline infused between two voiding cycles, and micturition volume (MV). Changes in frequency and amplitude of spontaneous non-voiding bladder contractions (NVC) were also recorded. The effects of the intravenous administration of suramin (100 mg/kg), BMY 7378 (1 mg/kg), and terazosin (0.3 mg/kg) on NVC, BVC and MV were evaluated in obstructed rats with bladder infusion of saline. The effects of infravesical infusion of suramin (3-10 micromol/L), terazosin (1 micromol/L) and BMY 7378 (10 micromol/L) were also evaluated and compared with values observed in control rats during saline infusion into the bladder. RESULTS: Intravenous injection with suramin had no effects on NVC, BVC and MV, but suramin infused into the bladder induced a consistent reduction in the amplitude of NVC (significantly different from matched control animals) with a tendency to reduce their frequency. BVC and MV were slightly but significantly decreased by infravesical infusion of suramin. In contrast, BMY 7378 and terazosin, given intravenously, were extremely potent at inhibiting the frequency and amplitude of the NVC, but were inactive on NVC when infused into bladder. CONCLUSIONS: These findings confirm a role for alpha1-adrenergic receptors in bladder instability caused by bladder outlet obstruction. In addition, a purinergic neurotransmitter, presumably ATP, is shown to be involved.

Administration, Intravesical↗

MELD scoring system is useful for predicting prognosis in patients with liver cirrhosis and is correlated with residual liver function: a European study.

BACKGROUND: Indices for predicting survival are essential for assessing prognosis and assigning priority for liver transplantation in patients with liver cirrhosis. The model for end stage liver disease (MELD) has been proposed as a tool to predict mortality risk in cirrhotic patients. However, this model has not been validated beyond its original setting. AIM: To evaluate the short and medium term survival prognosis of a European series of cirrhotic patients by means of MELD compared with the Child-Pugh score. We also assessed correlations between the MELD scoring system and the degree of impairment of liver function, as evaluated by the monoethylglycinexylidide (MEGX) test. PATIENTS AND METHODS: We retrospectively evaluated survival of a cohort of 129 cirrhotic patients with a follow up period of at least one year. The Child-Pugh score was calculated and the MELD score was computed according to the original formula for each patient. All patients had undergone a MEGX test. Multivariate analysis was performed on all variables to identify the parameters independently associated with one year and six month survival. MELD values were correlated with both Child-Pugh scores and MEGX test results. RESULTS: Thirty one patients died within the first year of follow up. Child-Pugh and MELD scores, and MEGX serum levels were significantly different among patients who survived and those who died. Serum creatinine, international normalised ratio, and MEGX(60) were independently associated with six month mortality while the same variables and the presence of ascites were associated with one year mortality. MELD scores showed significant correlations with both MEGX values and Child-Pugh scores. CONCLUSIONS: In a European series of cirrhotic patients the MELD score is an excellent predictor of both short and medium term survival, and performs at least as well as the Child-Pugh score. An increase in MELD score is associated with a decrease in residual liver function.

Adult↗

Platelet count/spleen diameter ratio: proposal and validation of a non-invasive parameter to predict the presence of oesophageal varices in patients with liver cirrhosis.

BACKGROUND AND AIMS: Cirrhotic patients frequently undergo screening endoscopy for the presence of oesophageal varices (OV). In the future, this social and medical burden will increase due to the greater number of patients with chronic liver disease and their improved survival. In this study, our aims were (1) to identify clinical, biochemical, and ultrasonographic parameters which might non-invasively predict the presence of OV in patients with liver cirrhosis; (2) to evaluate the reproducibility of the obtained results in a different, although related, further group of patients; and (3) to assess the predictiveness of the identified rules in patients with compensated cirrhosis. METHODS: In the first part of the study we retrospectively evaluated the presence of OV in 145 cirrhotic patients, and in the second part we evaluated the reproducibility of the study results in a subsequent group of 121 patients. Finally, we evaluated these parameters in a subgroup of 145 patients with compensated disease. All 266 patients underwent a complete biochemical workup, upper digestive endoscopy, and ultrasonographic measurement of spleen bipolar diameter. Platelet count/spleen diameter ratio was calculated for all patients. RESULTS: The prevalence rates of OV were 61% and 58% in the first and second groups of patients, respectively. In the first part of the study, we found that platelet count, spleen diameter, platelet count/spleen diameter ratio, and Child- Pugh class were significantly different among patients with or without OV, although the platelet count/spleen diameter ratio was the only parameter which was independently associated with the presence of OV in a multivariate analysis. A platelet count/spleen diameter ratio cut off value of 909 had 100% negative predictive value for a diagnosis of OV. This result was reproduced in the second group of patients as well as in patients with compensated disease. In a cost-benefit analysis, screening cirrhotic patients according to the "platelet count/spleen diameter ratio strategy" was far more cost effective compared with the "scope all strategy". CONCLUSIONS: The platelet count/spleen diameter ratio is the only parameter which is independently associated with the presence of OV, and its negative predictive value is reproducible. Its use is of value even in the subgroup of patients with compensated disease, and it is also cost effective.

Adult↗

13C-aminopyrine breath test to evaluate severity of disease in patients with chronic hepatitis C virus infection.

BACKGROUND: There are few data on the use of the 13C-aminopyrine breath test to evaluate the severity of disease in patients with hepatitis C virus-related chronic liver disease, although these patients represent one of the most important problems in clinical hepatology. AIMS: To compare 13C-aminopyrine breath test results of patients with hepatitis C virus-related chronic hepatitis and Child-Pugh class A cirrhosis with those of normal subjects, and to evaluate different methods of expressing 13C-aminopyrine breath test results. METHODS: Twenty-four patients with hepatitis C virus-related chronic hepatitis and 17 patients with Child-Pugh class A cirrhosis underwent 13C-aminopyrine breath test. Breath samples were collected every 30 min up to 2 h after 13C-aminopyrine administration. 13C-Aminopyrine breath test results were expressed as a percentage of the administered dose of 13C recovered per hour (% dose/h) and the cumulative percentage of administered dose of 13C recovered over time (% dose cum). Nineteen healthy subjects served as controls. Patients with hepatitis C virus-related chronic hepatitis were divided into subgroups on the basis of histological staging and grading. RESULTS: The 13C-aminopyrine breath test result (% dose/h) at 30 min was significantly different among the three subgroups of subjects (normal subjects, 11.5 +/- 3.5; chronic hepatitis patients, 8.1 +/- 4.1; cirrhosis patients, 5.0 +/- 3.1; P < 0.0005). Moreover, the differences between chronic hepatitis and cirrhosis patients were statistically significant (P < 0.03). The fibrosis score showed a significant inverse correlation with the 13C-aminopyrine breath test result (% dose/h) at 30 min (rs=- 0.409, P=0.05). The 13C-aminopyrine breath test result (% dose/h) at 30 min also allowed normal subjects and chronic hepatitis patients with low (< or = 2) or high (> 2) fibrosis scores to be distinguished. The 13C-aminopyrine breath test results (% dose cum) at 30, 60 and 90 min allowed discrimination between normal subjects and chronic hepatitis and cirrhosis patients. The 13C-aminopyrine breath test result (% dose cum) was also able to distinguish between normal subjects and chronic hepatitis patients with high but not low fibrosis scores. Both 13C-aminopyrine breath test results (% dose/h and % dose cum) at 120 min allowed the differentiation between normal subjects and chronic hepatitis patients with high (> or = 6) necro-inflammatory activity. CONCLUSIONS: In patients with hepatitis C virus-related chronic liver disease, the 13C-aminopyrine breath test proved to be safe and easy to perform, and was able to evaluate different degrees of liver function impairment which were partly correlated to clinical and histological evaluation. In future studies, 13C-aminopyrine breath test results should be expressed in a standardized fashion to permit comparison.

Aminopyrine↗

Helicobacter pylori masks differences in homocysteine plasma levels between controls and type 2 diabetic patients.

BACKGROUND: Data in the literature have not clarified whether type 2 diabetes mellitus affects homocysteine plasma levels. Different variables able to influence homocysteine could be the cause of these controversial findings. An important but neglected confounding factor is Helicobacter pylori, which has been demonstrated to be a cause of elevated levels of homocysteine and which is prevalent in the Caucasian population, ranging from 30 to 40% incidence. Starting from these findings we wanted to verify whether differences in homocysteine levels exist between a type 2 diabetic population and a control group, taking into account the presence/absence of Helicobacter pylori. DESIGN: The study was carried out on a group of uncomplicated and normotensive type 2 diabetic patients (n = 30, 55.7 +/- 9.7 years) and on a control group (n = 43, 51.2 +/- 11.3 years). On these subjects we evaluated: main parameters of glyco- and lipo-metabolic balance, presence of Helicobacter pylori by 13C Urea Breath Test, plasma homocysteine, vitamin B12, folate and genetic polymorphism of methylenetetrahydrofolate reductase. RESULTS: Evaluating the two groups as a whole, significant differences in homocysteine were found when considering Helicobacter pylori presence/absence (14.0 +/- 6.5 vs. 10.6 +/- 4.7 micromol L-1, respectively, P < 0.01) without differences of vitamins and the genetic polymorphism of methylenetetrahydrofolate reductase. The positive interaction found among Helicobacter pylori, diabetes and homocysteine (P = 0.03) taking into account all the other evaluated confounding factors, demonstrates that a significant difference in homocysteine plasma levels exists between diabetics and controls (Helicobacter pylori-negative: diabetics 12.5 +/- 5.6 micromol L-1, controls 9.4 +/- 3.8 micromol L-1; Helicobacter pylori-positive: diabetics 13.6 +/- 5.8 micromol L-1, controls 14.3 +/- 7.0 micromol L-1). CONCLUSIONS: Type 2 diabetes seems to induce per se higher levels of homocysteine, which appears to be one of the factors responsible for the increased risk of vascular damage.

Adult↗

trans-4-[4-(Methoxyphenyl)cyclohexyl]-1-arylpiperazines: a new class of potent and selective 5-HT(1A) receptor ligands as conformationally constrained analogues of 4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]-1-arylpiperazines.

The present paper concerns the influence of conformational parameters on the recognition by rat 5-HT1A receptors of derivatives 4-[3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)propyl]-1-(2-pyridinyl)piperazine (1a) and 3-(5-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)-N-[2-(2-pyridyloxy)ethyl]propanamine (3b), two highly potent and selective 5-HT1A receptor ligands. Fifteen corresponding flexible and rigid analogues were prepared following several synthetic routes and were tested in binding assays with radioligands at 5-HT1A, D2, and alpha1 receptors from rat brain membranes. Among the new derivatives emerged trans-4-[4-(3-methoxyphenyl)cyclohexyl]-1-(2-pyridinyl)piperazine (trans-8a) and trans-N-[4-(3-methoxyphenyl)cyclohexyl]-2-(2-pyridyloxy)ethylamine (trans-8b). These compounds can be considered as conformationally constrained analogues of compounds 1a and 3a, respectively. In fact, compounds trans-8a and trans-8b showed a marked enhancement in 5-HT1A receptor affinity when compared to the corresponding cis isomers. Because compound trans-8a was a potent and selective 5-HT1A ligand (K(i), nM: 5-HT1A = 0.028, D2 = 2194, alpha1 = 767), it was chosen as a lead to prepare other analogues that were tested at 5-HT1A, D2, and alpha1 receptors from rat brain membranes, showing high affinity at the 5-HT1A and selectivity vs D2 and alpha1 receptors. Selected compounds were tested for their affinity at the human cloned 5-HT1A, alpha1a, alpha1b, alpha1d receptor subtypes. They were also submitted to the [35S]GTPgammaS binding assay stimulating the 5-HT1A receptor-mediated G-protein activation, therefore behaving as full or as partial agonists. Finally, the ability of iv administration of trans-8a to induce fore-paw treading in rats was evaluated in comparison with 8-OH-DPAT. Although the affinity (K(i)) and in vitro activity (pD'2) of trans-8a at the 5-HT1A receptor were higher than those of 8-OH-DPAT, the compound was less potent than the reference standard in inducing the symptom.

Animals↗

In vitro and in vivo uroselectivity of B8805-033, an antagonist with high affinity at prostatic alpha1A- vs. alpha1B- and alpha1D-adrenoceptors.

We have investigated the pharmacological properties of B8805-033 [(+/-)- 1,3,5-trimethyl-6-[[3-[4-((2,3-dihydro-2-hydroxymethyl)-1,4-benzodioxin-5-yl)-1-piperazinyl]propyl] amino]-2,4(1H,3H)-pyrimidinedione], a new alpha1A-adrenoceptor (AR) selective antagonist. In radioligand binding studies, B8805-033 was 150- to 1200-fold selective for alpha1A-ARs (pKi rat cerebral cortex 8.70, cloned human receptor 7.71) relative to alpha1B-ARs (pKi rat cerebral cortex 5.60, rat liver 5.39, cloned human receptor 5.16) and alpha1D-ARs (pKi cloned human receptor 5.49). B8805-033 inhibited noradrenaline (NA) induced contractions mediated by alpha1A-ARs in rat vas deferens and rabbit and human prostate (pA2 7.62-8.40) much more potently than those mediated by alpha1B-ARs in guinea pig and mouse spleen or by alpha1D-ARs in rat aorta and pulmonary artery (pA2 5.21-5.52). With the exception of a high agonist affinity at 5-HT1A receptors (pKi 9.74 in pig cortex, pD2 6.82 for contraction of rabbit basilar artery) and a moderate to low affinity at histamine H1-receptors (pA2 6.74) and beta1-ARs (pA2 5.75), B8805-033 did not interact with a number of other neurotransmitter receptors (pKi or pA2<5.0). From the i.v. doses of B8805-033 to either inhibit the urethral pressure response to NA by 50% (29 nmol/kg) or to evoke a fall in diastolic blood pressure by 25% (1.54 micromol/kg) in anaesthetized dogs, an urethral/ vascular selectivity ratio of 52 was obtained, far exceeding that found for the nearly unselective prazosin (ratio 1.8). We conclude that B8805-033 is a highly alpha1A-AR selective antagonist, which may potentially be useful as pharmacological tool to investigate alpha1-AR heterogeneity and in the treatment of benign prostatic hyperplasia.

Adrenergic alpha-Antagonists↗

Relationship between lipoprotein(a) levels, oxidative stress, and blood pressure levels in patients with essential hypertension.

High plasma levels of lipoprotein(a) [Lp(a)] are considered a risk factor for the development of coronary artery disease. In vitro experiments have shown that oxidized Lp(a) is able to impair the arterial endothelium-dependent dilation, thus suggesting a possible role of Lp(a) in the genesis of essential hypertension. The aim of our work was to investigate the correlation of blood pressure levels with plasma Lp(a) concentration, apo(a) isoform size, and peroxidative stress in patients with essential hypertension. The study was performed in 54 untreated hypertensive patients whose blood pressure was monitored for 24 h by ambulatory blood pressure monitoring. Lp(a) concentration was measured by a double monoclonal antibody-based enzyme immunoassay demonstrated to be insensitive to apo(a) size heterogeneity. Apo(a) isoforms were determined by a high-resolution SDS-agarose gel electrophoresis followed by immunoblotting. A significant correlation was found between Lp(a) levels and the night-time systolic and diastolic pressures (r=0.32, P<0.05 and r=0.30, P<0.05, respectively), as well as with the mean night-time fall in systolic and diastolic blood pressures (r=-0.28, P<0.05 and r=-0.29, P<0.05, respectively). These relationships were further potentiated when peroxidative stress data were taken into consideration (r=0.37 and r=0.40, P<0.01 for the night-time systolic and diastolic pressures, respectively and r=-0.34 and r=-0.38, P<0.01 for the night-time fall in systolic and diastolic blood pressures, respectively). Apo(a) isoform size did not affect these relationships. Our data suggest that Lp(a) and peroxidative stress may be involved as cofactors in essential hypertension, with a mechanism that remains to be elucidated.

Adult↗

Fast, simple and cost-effective determination of thiopental in human plasma by a new HPLC technique.

BACKGROUND: Thiopental is an anaesthetic drug that is largely used in both short-term and long-term infusion. After long-term infusion of thiopental, non-linear and inter-individual-dependent pharmacokinetics occur because of the saturation and/or induction of the metabolism. Clinical monitoring is important so that therapeutic adjustments can be made in many of the different pharmacological treatments, especially when long-term infusion is required. We describe a new, rapid HPLC method for the determination of plasma thiopental. METHODS: Sample preparation involved precipitation of plasma proteins using a mixture of methanol, zinc sulfate and ethylene glycol, and containing the internal standard 5-ethyl-5-p-tolyl-barbituric acid. After adding trichloroacetic acid, the sample was centrifuged and the supernatant was injected into a C(18) reversed-phase column. The mobile phase used was water-methanol-acetonitrile (50:40:10, v/v). The eluent was monitored at 290 nm. RESULTS: The calibration curve was linear from 0.2 to 100 microg/mL. Precision, calculated as the coefficient of variation (%), was in the range of 3.62-0.70% for the within-day assay and 5.77-1.51% for the between-day assay. The absolute recoveries obtained from supplemented samples were never less than 100%. CONCLUSIONS: This technique shows good reliability and seems to be suitable for a very fast and simple therapeutic monitoring of plasma thiopental.

Anesthetics, Intravenous↗

Increased levels of gammaGT suggest the presence of bile duct lesions in patients with chronic hepatitis C: absence of influence of HCV genotype, HCV-RNA serum levels, and HGV infection on this histological damage.

Damage to bile ducts in chronic hepatitis C is a characteristic histological lesion. Moreover, the presence of abnormal levels of gammaGT in these patients is also a common finding. Assessing whether the presence of bile duct lesions is indicated by biochemical abnormalities or whether virological characteristics can influence their development may help in the definition of clinical-histological relationships in chronic hepatitis C. In this study we evaluated the relationships among routine biochemical parameters, serum bile acids, and pi-class glutathione S-transferase levels, and the presence of bile duct lesions in 60 patients with chronic hepatitis C. Furthermore, we assessed whether the presence of bile duct lesion might be related to HCV genotype, HCV-RNA serum levels, and positivity for HGV-RNA. We found that gammaGT was the only parameter related to the presence of bile duct lesions. Although a trend towards higher serum bile acids and pi-class glutathione S-transferase levels was observed in patients with bile duct lesions, this trend did not reach statistical significance. Different HCV genotypes and RNA levels, and HGV-RNA positivity did not seem to influence the presence of bile duct damage. In conclusion we found that gammaGT levels point out the presence of bile duct lesions in patients with chronic hepatitis C. Since we observed a different pattern of alteration of gammaGT, serum bile acids, and pi-class glutathione S-transferase, we suggest that these various biochemical alterations reflect a more complex damage to bile duct structures, which is not likely represented by the common assessment of bile duct lesions. Viral factors such as HCV genotype and RNA levels as well as HGV-RNA positivity are probably not the main cause of this histological damage.

Adult↗

Impairment of cytochrome P-450-dependent liver activity in cirrhotic patients with Helicobacter pylori infection.

BACKGROUND: Helicobacter pylori gastric infection has been associated with various digestive and extra-digestive diseases. The systemic influence of gastric H. pylori infection seems to be mediated by the release of various cytokines. In liver disease, bacterial infections have been associated with the impairment of liver metabolic function. AIMS: To evaluate the influence of H. pylori infection on liver function as assessed by means of the monoethylglycinexylidide test, which depends upon liver blood flow and cytochrome P-450 activity, and the 13C-galactose breath test, which depends on cytosolic enzymatic activity and is correlated with hepatic functional mass. Moreover, to evaluate whether H. pylori-associated modifications of liver function may be related to tumour necrosis factor-alpha serum levels. PATIENTS AND METHODS: Thirty-five patients with liver cirrhosis of various aetiologies, who underwent monoethylglycinexylidide and 13C-galactose breath tests, were retrospectively evaluated for H. pylori infection by means of anti-H. pylori immunoglobulin G. The main clinical, biochemical and functional characteristics of the patients as well as their tumour necrosis factor-alpha serum levels were then analysed on the basis of the presence of H. pylori infection. RESULTS: Twenty-one patients tested positive for H. pylori infection (60%), and 11 tested negative (31.4%). No clinical or biochemical differences were observed between H. pylori-infected and non-infected patients. H. pylori infection showed no difference in distribution according to Child-Pugh classes (A, 55%; B and C, 67%). The monoethylglycinexylidide test results were significantly lower at each sampling time in H. pylori-positive patients compared to H. pylori-negative patients (MEGX15, P=0.027; MEGX30, P=0.014; MEGX60, P=0.028), while 13C-galactose breath test showed no significant differences considering both cumulative percentage dose and percentage dose/h. The median tumour necrosis factor-alpha serum levels were no different between H. pylori-positive (16.1 pg/mL, 95% confidence interval, 8.7-28.7) and H. pylori-negative (12.3 pg/mL, 95% confidence interval, 8.7-23.4) patients. CONCLUSIONS: In cirrhotic patients, H. pylori infection seems to selectively affect cytochrome P-450 liver activity, while hepatic functional mass does not seem to be impaired. Tumour necrosis factor-alpha does not seem to be the mediator of this impairment. Further studies are needed to evaluate the impact of H. pylori eradication on parameters of liver function.

Aged↗

Long-term follow up of chronic hepatitis C patients after alpha-interferon treatment: a functional study.

AIM: To evaluate the long-term functional outcome of chronic hepatitis C (CHC) patients treated with interferon (IFN) therapy. METHODS: Thirty-six patients with CHC were followed up for a mean of 36 months (+/- 19, SD) after a course of IFN therapy. Biochemical, virological (qualitative hepatitis C virus (HCV)-RNA and HCV genotype), and functional (monoethylglycinexylidide (MEGX) test) evaluations were carried out at the time of liver biopsy. Patients were divided into long-term responders (LTR), relapsers (RR), or non-responders (NR) according to IFN therapy outcome. At the end of follow up, patients were non-invasively re-evaluated by means of biochemistry, qualitative HCV-RNA, MEGX test, and liver ultrasonography. RESULTS: A significant decrease in MEGX values was observed in all patients. However, when patients were examined according to treatment outcome, only NR and RR showed a significant decrease in liver function as compared to pretreatment levels (MEGX30, 80.5 +/- 26.8-62.9 +/- 24.2 ng/mL, P< 0.01; MEGX60, 72.9 +/- 18.1-60.5 +/- 19.7 ng/mL, P< 0.05; MEGXAUC, 3,816 +/- 1,243-3,095 +/- 1,205 ng/mL per h, P< 0.05). On the contrary, LTR patients showed no significant modifications in MEGX values at each sampling time (MEGX,5, 72.9 +/- 31.4-70.3 +/- 29.7 ng/mL; MEGX30, 84.0 +/- 27.6-71.5 +/- 21.8 ng/ mL; MEGX60, 69.5 +/- 26.8-63.2 +/- 14.4 ng/mL; MEGXAUC 4028 +/- 1,378-3,620 +/- 1,041 ng/mL per h). At the end of follow up, LTR patients showed normal liver biochemistry and negativity of serum HCV-RNA, while NR and RR patients showed a significant decrease in platelets. CONCLUSIONS: In CHC patients long-term response to IFN therapy, besides favoring positive clinical and virologic long-term outcome, results in maintaining preserved liver function. Furthermore, IFN therapy seems to determine a decrease in the rate of functional disease progression, even in NR and RR. The MEGX test may be considered as a useful tool for performing serial follow up of CHC patients.

Adult↗