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Biomedical subjects

S Restuccia

Publications and source records attributed to S Restuccia.

12 recordsLinked to original sources

Antiviral drugs in chronic hepatitis B: review and meta-analysis.

Many researchers have attempted to identify the drugs capable of acting on the viral replication cycle and maintaining clinical remission in chronic hepatitis B. We evaluated the efficacy of antiviral drugs in chronic hepatitis B, by examination of 20 controlled and non-controlled trials conducted between 1985 and 1996. In chronic hepatitis B, adenine arabinoside and its monophosphate did not achieve satisfactory results, even though combination therapy with cortisone seemed to achieve very good results (remission rates ranging from 45% to 66% in patients treated). Lamivudine did not seem to furnish lasting effects in chronic hepatitis B, because many patients relapse after suspension of the treatment due to the appearance of HBV variants resistant to the drug. Contrasting results were observed with famciclovir. Treatment of chronic hepatitis B, with this drug seemed capable of reducing HBV-DNA serum levels by a mean of 50% compared to pretreatment values, with normal alanine aminotransferase levels in about 30% of treated patients. Ganciclovir treatment of chronic hepatitis B seemed to furnish good, but transient, results. Even if no antiviral drug represented a valid alternative to interferon, antivirals may become the drugs of choice in chronic hepatitis B, because they are aimed at the etiology of disease.

Antiviral Agents↗

5-fluorouracil alone versus 5-fluorouracil plus folinic acid in the treatment of colorectal carcinoma: meta-analysis.

OBJECTIVE: Innovative techniques in the field of artificial intelligence could help to resolve several methodological problems. A model taking into account all the parameters involved in a therapy can foresee the results of each type of treatment or therapeutic protocol on patients at different stages of a disease. We used a Computer Decision Support System in order to verify the reliability and efficacy of this method on chemotherapy of colorectal carcinoma. MATERIAL AND METHODS: We analyzed 8 randomized clinical trials employing 5-fluorouracil alone (5-FU) or 5-fluorouracil (5-FU) plus leucovorin (FA) in the management of advanced colorectal carcinoma. Computer Decision Support System (CDSS) was used to perform four basic tasks: data acquisition and organization; data recruitment; combination of the various principles and specific data; user-friendly display of the analysis results and responses to treatment. RESULTS: In the majority of the studies examined, the death rates were lower in patients treated with 5-FU + FA than in those on 5-FU alone, even though the difference was not statistically significant. However, there were wide fluctuations in the efficacy/tolerability ratio between the two protocols investigated, depending on the patients' clinical status. Our data showed that a strong attack using 5-FU + FA is feasible whenever the patients' clinical conditions are not particularly severe, whereas a moderate attack using 5-FU alone is recommended as the patients' clinical condition worsens. CONCLUSION: The use of CDSS in the management of colorectal carcinoma indicates which therapy is the best in terms of efficacy, overall survival and incidence of side effects.

Antimetabolites, Antineoplastic↗

Rapid evolution of chronic viral hepatitis into hepatocellular carcinoma after beta-interferon treatment.

A 62-year-old man, affected by Chronic Active Hepatitis (discovered in 1993) and treated with interferon, referred to our department with increased abdominal volume, persistent abdominal pain, continuous-remittent fever and jaundice. CT scan of the liver revealed a hypodense, not capsulated, infiltrative, solid formation in the right lobe. US guided biopsy showed multinucleated giant cells, with eosinophilic cytoplasm and pleomorphism of the nuclei, arranged in several thick trabecula lined by endothelial cells or formed bile containing acini. In our case, the rapid evolution of chronic viral hepatitis towards HCC calls for a careful evaluation of the role of IFN therapy, since this drug is widely used in chronic liver diseases.

Antiviral Agents↗

Interferon alpha-induced depression in chronic hepatitis C patients: comparison between different types of interferon alpha.

IFN alpha treatment is able to produce dose-related side effects, such as depression, in the central nervous system. We assessed the effects on depression of four different types of IFN alpha (recombinant IFN alpha 2a, recombinant IFN alpha 2b, lymphoblastoid IFN alpha, leukocyte IFN alpha), administered at the same doses in four homogeneous groups of chronic hepatitis C patients (96 patients; 24 patients for each group). A group of 18 untreated hepatitis C patients was considered as a control group. Depression was measured using Zung's self-rating depression scale (SDS scale) before starting IFN alpha therapy and at the 1st, 3rd and 6th month of treatment. In all patients evaluated, mean SDS values increased from mild to moderate depression, but never attained severe depression (SDS > 70). More elevated SDS values were observed in the 1st month of treatment, with a progressive decrease during the end points above-mentioned. The recombinant IFN alpha 2a and lymphoblastoid IFN alpha arms presented higher SDS mean scores compared to the recombinant IFN alpha 2b and leukocyte IFN alpha arm. Only in the leukocyte IFN alpha arm SDS values returned to basal values at the 6-month end point. Leukocyte IFN alpha seemed to present a more elevated tolerability than other IFN alpha types available for clinical practice. A very careful selection of hepatitis C patients is required before starting IFN alpha therapy.

Aged↗

Efficacy of different schedules in the management of chronic hepatitis C with interferon-alpha.

The best results in terms of clinical remission in chronic hepatitis C are achieved by interferon (IFN)-alpha treatment. We studied 255 patients affected by chronic hepatitis C infection (HCV) and divided into 3 groups. A different IFN-alpha therapeutic schedule was adopted in each group: A) 3 million units (MU) three times per week for 6 months; B) 3 MU three times per week for 12 months; C) 6 MU three times per week for 6 months. A sustained biohumoural and virological remission was observed in only 14.5% of the patients included in group A, in 21.6% of the patients included in group B and in 8% of the patients included in group C. The adoption of more aggressive therapeutic regimens did not offer an improvement in response or patient compliance. At present, the long term efficacy of treatment may be evaluated on the basis of both biochemical and virological data.

Adolescent↗

Elevation of interleukin 6 levels in patients with chronic hepatitis due to hepatitis C virus.

Interleukin 6 (IL-6) is a pleiotropic cytokine produced by a wide variety of lymphoid and non-lymphoid tissues. We studied the relationship between IL-6 and the liver in an attempt to elucidate this cytokine's role in hepatitis C-induced liver inflammation. We investigated the behavior of serum IL-6 in 25 patients with chronic hepatitis C (divided into three groups depending on severity) and in 27 healthy controls. Our results showed a significant elevation (P < 0.0001) in serum IL-6 levels in the patients with chronic hepatitis C, correlated with the histological activity index (HAI) and their HCV-RNA serum levels. This rise may represent the expression of the hepatitis C virus-induced inflammatory state.

Case-Control Studies↗

Decrease of interferon gamma serum levels in patients with chronic hepatitis C.

Cytokines can play a crucial role in defending the organism from viral infections. One of these, interferon gamma (IFN-gamma), possesses marked immunomodulating activity. As cell immunity seems to be involved in chronic hepatitis C virus (HCV), study of the events regulated by IFN-gamma may be useful in evaluating the host's immunological response. We studied 63 patients (36 males, 27 females) affected by chronic HCV and 28 (14 males, 14 females) healthy controls. IFN-gamma concentrations were significantly lower in the former, and were positively correlated with the histological activity index, suggesting that low IFN-gamma values play a part in determining chronicity. We believe they may be an unfavorable factor and may be useful in detecting patients who are not capable of eradicating the virus.

Adult↗

Serum beta2-microglobulin in chronic hepatitis C.

beta2-Microglobulin (beta2-MG) plays a key role in influencing the immune response to viral infections as it is an integrating part of the main histocompatibility system (HLA). We attempted to evaluate the changes in class I HLA antigens by comparing the serum beta2-MG behavior in a group of patients affected by chronic hepatitis C with that observed in a group of healthy controls. Our study revealed that the patients presented higher serum beta2-MG levels than healthy controls (P = 0.0003). beta2-MG levels were correlated with duration and degree of the disease. Furthermore, there was a statistically significant correlation between beta2-MG and HCV RNA levels, while no correlations were observed between serum beta2-MG levels and HCV genotypes. The increment in serum beta2-MG values accompanying the progression of liver disease may be an expression of augmented production rather than altered excretion.

Adult↗

Mapped auditory evoked potentials before and after interferon treatment.

Neurotoxicity induced by interferon (IFN) is revealed by neurobehavioral changes, such as irritability, somnolence, lack of motivation, and delayed ideation. As these side effects persist throughout IFN-alpha treatment, we studied cerebral mapped auditory evoked potentials (MAEP) in 20 hepatitis C virus antibody (HCV Ab)-positive chronic active hepatitis patients before and after administration of leukocyte IFN-alpha (i.m. 3,000,000 IU). Some of the main components of MAEP, such as morphology, latency, and power spectra, were altered before IFN injection. These parameters changed 7 h after administration as revealed by increased quality and quantity of acoustic signal reaching the brain cortex and appearance of physiologic waves in patients with mild/intermediate liver disease. These effects revealed 48 h after IFN administration.

Adult↗

Treatment of nonresectable hepatocellular carcinoma: review of the literature and meta-analysis.

Many doubts surround the numerous forms of nonsurgical treatment of nonresectable hepatocellular carcinoma (HCC). Our study aimed to reach reliable conclusions on the actual efficacy of these treatments. We examined 85 studies involving a total of 6746 patients: 6113 were treated; the remaining 633 were not. We applied the Mantel-Haenszel-Peto method to the extrapolated data, based on the reported 1- and 3-year survival rates. The results confirm that percutaneous ethanol injection achieved survival exceeding 5 years in many cases of HCC characterized by small nodules (diameter < 3 cm). The most efficacious nonsurgical treatment options were transcatheter arterial embolization and transcatheter arterial chemoembolization. Systemic chemotherapy and hepatic intra-arterial chemotherapy were not very effective.

Adult↗

A meta-analysis of interferon-alpha treatment of hepatitis D virus infection.

The severity of chronic hepatitis D infection and its unfavorable progress necessiate research into drugs and protocols capable of changing the natural history of the disease. Over the last few years interferon (IFN)-alpha has been the drug of choice in the management of this infection. We assessed its long-term efficacy by analyzing 5 controlled and 10 uncontrolled trials conducted between 1987 and 1994. The Mantel-Haenszel-Peto method was used in the former to perform statistical analysis. The odds ratio (0.16, confidence interval 0.058-0.476) confirmed the efficacy of IFN-alpha, even if the coefficient was not significant because of the limited number of spontaneous remissions in the trials. Although IFN treatment is fully beneficial in only a small number of patients with chronic hepatitis D infection, at present it is the only available agent.

Antiviral Agents↗

Interferon, cortisone, and antivirals in the treatment of chronic viral hepatitis: a review of 30 years of therapy.

Over the last 30 years many approaches have been adopted to treat chronic hepatitis. We conducted a meta-analysis to assess the efficacy of various types of treatments. We selected 4 studies of cortisone in chronic hepatitis B; 21 trials of interferon treatment, 6 in chronic hepatitis B, 10 in chronic hepatitis C, and 5 in chronic hepatitis D; and 5 of combined cortisone and interferon treatment in chronic hepatitis B. The Mantel-Haenszel-Peto method was applied to extrapolated data. We completed the study by analyzing four studies of cortisone treatment of chronic hepatitis C, two of cortisone plus interferon alpha (IFN-alpha) for chronic hepatitis C, and antiviral therapy for hepatitis B, C, and D. Trials administering cortisone for chronic hepatitis B had an overall OR of 0.29 (CI 0.12-0.73). No virologic remissions were observed in patients with hepatitis C receiving prednisone, even if those with features of autoimmunity achieved a biohumoral sustained response. Overall ORs in the trials were were as follows: IFN for chronic hepatitis B, 0.27 (CI 0.17-0.46); IFN for chronic hepatitis C, 0.3 (CI 0.21-0.44); IFN for chronic hepatitis D, 0.16 (CI 0.06-0.47); and cortisone plus interferon for chronic hepatitis B, 0.25 (CI 0.15-0.41). Sustained response rates of chronic hepatitis C ranged from 15-24.2%. The only encouraging results were obtained by antivirals. To date the lack of a specific antiviral drug makes it uncertain as to the preferred agent for this disease.

Anti-Inflammatory Agents↗