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P Andreone

Publications and source records attributed to P Andreone.

At least 19 recordsLinked to original sources
PubMed2006

Review article: alcoholic liver disease--pathophysiological aspects and risk factors.

BACKGROUND: Alcoholic liver disease has a known aetiology but a complex and incompletely known pathogenesis. It is an extremely common disease with significant morbidity and mortality, but the reason why only a relatively small proportion of heavy drinkers progress to advanced disease remains elusive. AIM: To recognize the factors responsible for the development and progression of alcoholic liver disease, in the light of current knowledge on this matter. METHODS: We performed a structured literature review identifying studies focusing on the complex pathogenetic pathway and risk factors of alcoholic liver disease. Results In addition to the cumulative amount of alcohol intake and alcohol consumption patterns, factors such as gender and ethnicity, genetic background, nutritional factors, energy metabolism abnormalities, oxidative stress, immunological mechanisms and hepatic co-morbid conditions play a key role in the genesis and progression of alcoholic liver injury. CONCLUSIONS: Understanding the pathogenesis and risk factors of alcoholic liver disease should provide insight into the development of therapeutic strategies.

Alcohol Drinking↗
PubMed2006

Low replication and variability of HBV pre-core in concomitant infection with hepatitis B and hepatitis C viruses.

In an attempt to define the virological profile of HBV in HCV co-infection, we analysed the viral load, the infecting genotype, and the mutational pattern of the HBV pre-core region (pre-C), which is involved in viral encapsidation and DNA replication. Eighty-six patients were studied: 32 with serological HBV/HCV-1b co-infection (group BC), 32 infected by HBV alone (group B), and 22 by HCV-1b alone (group C). Sequence analysis of the HBV pre-S and pre-C regions identified genotypes and mutational patterns. The HBV viral load was significantly lower in group BC than in group B (p < 0.001), and the distribution of HBV pre-C mutations showed a higher prevalence of wild type in concomitant infection than in the control group (p < 0.006). The predominant HBV infecting strain was genotype D in both the BC (96%) and B (87%) groups. No difference was observed in HCV viremia levels between the two groups, whereas in HBV/HCV infection, the low levels of circulating HBV were closely associated with the low degree of variability of pre-C domain (p = 0.005). In conclusion, in HBV/HCV infection, the virological pattern was characterised by the dominance of HCV associated with lower HBV replication capacity and decreased emergence of HBV pre-C variants.

DNA, Viral↗
PubMed2006

High incidence of allograft dysfunction in liver transplanted patients treated with pegylated-interferon alpha-2b and ribavirin for hepatitis C recurrence: possible de novo autoimmune hepatitis?

BACKGROUND: Interferon may trigger autoimmune disorders, including autoimmune hepatitis, in immunocompetent patients. To date, no such disorders have been described in liver transplanted patients. METHODS: 9 of 44 liver transplanted patients who had been receiving pegylated-interferon alpha-2b and ribavirin for at least 6 months for hepatitis C virus (HCV) recurrence, developed graft dysfunction despite on-treatment HCV-RNA clearance in all but one case. Laboratory, microbiological, imaging and histological evaluations were performed to identify the origin of graft dysfunction. The International Autoimmune Hepatitis scoring system was also applied. RESULTS: In all cases infections, anastomoses complications and rejection were excluded, whereas the autoimmune hepatitis score suggested a "probable autoimmune hepatitis" (score from 10 to 14). Three patients developed other definite autoimmune disorders (overlap anti-mitochondrial antibodies (AMA)-positive cholangitis, autoimmune thyroiditis and systemic lupus erythematosus, respectively). In all cases, pre-existing autoimmune hepatitis was excluded. Anti-lymphocyte antibodies in immunosuppressive induction treatment correlated with the development of the disorder, whereas the use of granulocyte colony-stimulating factor to treat interferon-induced neutropenia showed a protective role. Withdrawal of antiviral treatment and treatment with prednisone resulted in different outcomes (five remissions and four graft failures with two deaths). CONCLUSIONS: De novo autoimmune hepatitis should be considered in differential diagnosis along with rejection in liver transplanted patients developing graft dysfunction while on treatment with interferon.

Aged↗
PubMed2006

Posttransplant lymphoproliferative disorders in liver transplanted patients: a report of four cases.

BACKGROUND: Posttransplant lymphoproliferative disorders (PTLDs) are an uncommon but important cause of morbidity and mortality in solid organ transplant recipients. They are often the result of Epstein-Barr virus (EBV)-induced proliferation of B-lymphocytes in the setting of immunosuppression. PATIENTS AND METHODS: We retrospectively analyzed four cases of PTLD after liver transplantation. In all patients immunosuppression was reduced and anti-CD20 monoclonal antibody (rituximab) was administered. In two of four patients, EBV viral load was positive in the peripheral blood, and gancyclovir was therefore also prescribed. Chemotherapy (CHOP) was used as a rescue in the event of treatment failure. RESULTS: Even if no severe adverse events were observed during the treatment period, our treatment approach to PTLD was not effective, and only one patient out of four is still alive. CONCLUSIONS: Well-designed clinical trials are necessary to evaluate the role of this combined approach in the treatment of PTLD in liver transplant recipients.

Aged↗
PubMed2006

Virological analysis, genotypes and mutational patterns of the HBV precore/core gene in HBV/HCV-related hepatocellular carcinoma.

We investigated the replicative profile of hepatitis B (HBV) and hepatitis C (HCV) viruses and the mutational pattern of the HBV precore/core (pre-C/C) domain in hepatocellular carcinoma (HCC). Thirty-eight consecutive patients with HCC were included in the study - 18 of them with HBV/HCV co-infection and 20 with HBV single infection. Twenty-three additional patients with co-infection, without HCC were recruited as the control group. Replication activity was evaluated by detecting and quantitating both HBV and HCV genomes. The HBV pre-C/C region, encompassing the pregenome encapsidation signal involved in viral replication, was analysed by direct sequencing. HBV viraemia levels were significantly lower (P = 0.04) in patients with co-infection in comparison with single-infected HCC, whereas two different HBV viraemia profiles were detected in co-infection with or without circulating HCV. HBV genotype D was prevalent in the three groups and HCV genotype 1b was found to be the infecting strain in all patients. Lower variability in the pre-C/C region was found in co-infection in comparison with HBV single infection (P = 0.0004). A synonymous T1936C mutation was found in all co-infected HCC cases not related to the presence or absence of circulating HCV, and a hypermutated pre-C strain, characterized by the same mutational pattern, was identified in three HCC cases. The mutational pattern of the pre-C/C region was closely related to HBV replication efficiency, and specific HBV mutations selectively associated with HCV co-infection could be linked with accelerated HBV/HCV-related disease progression.

Adult↗
PubMed2005

Pegylated interferon plus ribavirin for recurrent Hepatitis C infection after liver transplantation in naïve and non-responder patients on a stable immunosuppressive regimen.

BACKGROUND: Hepatitis C virus recurrence after liver transplantation is universal, leading to chronic hepatitis and cirrhosis. AIMS AND PATIENTS: We evaluated the efficacy and safety of pegylated interferon and ribavirin in 20 patients with recurrent Hepatitis C virus after liver transplantation (10 naïve and 10 non-responders to a previous interferon course). METHODS: Treatment consisted of pegylated interferon alfa-2b (1.0 microg/kg once weekly) and ribavirin (600 mg/daily) for at least 6 months. Therapy continued for an additional 6 months only in patients with undetectable serum Hepatitis C virus-RNA or >2 log drop from baseline levels. RESULTS: Eleven out of 20 patients (55%) completed 1 year of treatment. Nine patients (45%) had undetectable Hepatitis C virus-RNA at the end of treatment, six of them were naïves and three non-responders. In all of them, virological response persisted 6 months after discontinuation of therapy, so the sustained virological response rate was 60% in naïve patients and 30% in non-responders. CONCLUSIONS: Our results suggest that pegylated interferon plus ribavirin combination therapy may be effective in patients with post-liver transplantation recurrent chronic Hepatitis C, even in those previously non-responders to interferon plus ribavirin. These results need to be confirmed by large studies.

Aged↗
PubMed2005

Cytokine profile of peripheral blood mononuclear cells from patients with different outcomes of hepatitis C virus infection.

SUMMARY: The relationship between the balance of helper T-cell type 1 (Th1) or type 2 (Th2) cytokines and the clinical course of hepatitis C virus (HCV) infection is unclear. We evaluated Th1 [interleukin (IL)-2, interferon-gamma (IFN-gamma)] and Th2 cytokine (IL-4, IL-10) and 2,5-oligoadenylate synthetase (OAS, an IFN-induced antiviral protein) production by peripheral blood mononuclear cells from 10 healthy anti-HCV-positive individuals (group A), 10 HCV-RNA-positive with persistently normal alanine aminotransferase (ALT) levels (group B), 10 HCV-RNA-positive with abnormal ALT (group C) and 10 uninfected healthy controls. IL-2 production was significantly increased in group B when compared with all the other groups. No difference was found for IFN-gamma. IL-4 was significantly higher in group C than in both group B (P = 0.0006) and controls (P = 0.004). Compared with controls, IL-10 was significantly decreased in group A (P = 0.013) and B (P = 0.004). The production of 2,5-OAS was significantly higher in group B than in A (P = 0.04) and in C (P = 0.004). Finally, in all HCV-RNA-positive patients, a significant correlation was found between ALT and both IL-2 (r = -0.78; P = 0.0008) and IL-4 (r = 0.75; P = 0.0008). IN CONCLUSION: (i) subjects who cleared HCV showed a cytokine profile similar to controls; (ii) a preferential shift towards a Th1 profile seems associated with a more favourable clinical outcome in chronic hepatitis C; and (iii) a prevalent Th2 profile seems implicated in HCV pathogenesis and severity of liver disease.

Adult↗
PubMed2005

Human herpesvirus-8-related Kaposi's sarcoma after liver transplantation successfully treated with cidofovir and liposomal daunorubicin.

The iatrogenic form of Kaposi's sarcoma (KS) is typically observed among transplant recipients, and the most appropriate therapeutic approach (usually including reduction of immunosuppression, specific chemotherapy, and/or administration of antiviral agents against human herpes virus-8) is still controversial. Available experiences on the effect of the anti-herpes viruses drug cidofovir provide conflicting results. Herein, we report the clinical, histological, and virological features of a liver transplant recipient successfully treated with a combined therapy of cidofovir and liposomal daunorubicin, associated with a reduction of the immunosuppressive regimen, for an advanced cutaneous and visceral KS.

Antibiotics, Antineoplastic↗
PubMed2004

Genetic variability of hepatitis C virus in HBV/HCV co-infection and HCV single-infection.

To describe the virological profile of HCV in HBV/HCV co-infection, we investigated the variability of HVR-1 and NS5A domains, which may be involved in viral persistence and replication efficiency. We studied 95 patients: 37 with serological markers of HBV/HCV co-infection, 33 with single HBV and 25 with single HCV infection. HVR-1 complexity and NS5A gene variability were respectively explored by means of PCR-SSCP and direct sequencing. Serum HBV genomes were detected in all coinfected patients: 19 also had circulating HCV particles (group BC-I), whereas HCV were undetectable in the other 18 (group BC-II). Group BC-I was characterised by a significantly lower HBV replication capacity, that reflects the replicative dominance of HCV, although the dominant virus had the same degree of variability as the HCV in single infection. HBV viral load was higher in group BC-II, but not significantly different from that observed in the single infection. Our data indicate an alternation in replicative dominance in co-infection: HBV can suppress HCV replication to undetectable levels, whereas HCV may reduce but does not abrogate the replication capacity of HBV. Furthermore, in the cases of HCV dominance, circulating HBV genomes did not have a significant effect on the viral heterogeneity of HCV.

Adult↗
PubMed2004

Thymosin-alpha 1 plus interferon-alpha for naive patients with chronic hepatitis C: results of a randomized controlled pilot trial.

In this pilot study, we evaluated the efficacy of interferon-alpha (IFN) plus Thymosin-alpha 1 (TA1) to that of IFN alone in naive patients with chronic hepatitis C. Twenty-two patients were randomized to receive interferon-alpha 2b (3 million units three times a week) plus thymosin-alpha l (900 microg/m2 body surface area) and 19 received interferon-alpha 2b alone at the same dose. Patients were treated for 6 months and followed up for another 6 months. Biochemical (alanine aminotransferase values) and virological (hepatitis C virus-RNA) responses to treatment were determined. Combination treatment showed significantly higher efficacy than monotherapy in achieving virological end-of-treatment response (P = 0.03). At 6-month follow up, the sustained biochemical and virological response was not different between the two groups. Our results indicate that the immune modulator TA1 may enhance the end-of-treatment response in naive patients with chronic hepatitis C. Higher doses and/ore more prolonged courses as well as the association with new interferon formulation such as pegylated interferons could improve the sustained response rates to this treatment.

Adjuvants, Immunologic↗
PubMed2004

High risk of hepatocellular carcinoma in anti-HBe positive liver cirrhosis patients developing lamivudine resistance.

The emergence of drug-resistant virus in hepatitis B virus patients treated with lamivudine is well documented. However, its clinical impact in the long-term treatment of anti-HBe positive compensated cirrhotic patients is not well known. In this study, we treated 22 consecutive patients with anti-HBe compensated cirrhosis with lamivudine for a median period of 42 months. All patients responded to lamivudine, but viral breakthrough occurred in 13 patients (59%) between 9 and 42 months of therapy due to the emergence of a mutant strain. During the follow-up, 11 developed hepatocellular carcinoma. Of these, 10 occurred soon after the emergence of viral resistance, generally showing aggressive behaviour, and one in the nine long-term responder patients (P = 0.013). Lamivudine resistance was the only independent predictor of hepatocellular carcinoma development (risk ratio: 10.4; 95% CI: 1.3-84.9). Our study suggests that the occurrence of lamivudine resistance increases the risk of hepatocellular carcinoma in anti-HBe positive cirrhosis and warrants further research.

Adult↗
PubMed2003

Interferon-alpha combined with ketoprofen as treatment of naïve patients with chronic hepatitis C: a randomized controlled trial.

In this randomized controlled study, we evaluated the efficacy and safety of interferon-alpha combined with ketoprofen to that of interferon-alpha alone in naïve patients with chronic hepatitis C. Forty patients were randomized to receive Interferon-alpha2a (3 million units three times a week) and ketoprofen (150 mg twice a day) and 40 to receive only interferon-alpha2a at the same dose. Patients were treated for 6 months and followed up for 6 months. Response was defined by undetectable HCV-RNA in serum at the end-of-treatment and after 6 months from the completion of therapy (long term response). At the end of treatment the response was similar in the two group. However, combination treatment showed significantly higher efficacy than monotherapy in achieving long term response (10%vs 32.5%; P = 0.014). Overall adverse events were similar in the two groups. 'Flu-like syndrome was significantly less common in the ketoprofen plus interferon group which experienced a significantly higher incidence of epigastric pain'. Our results indicate that the combination of ketoprofen plus interferon is significantly more effective than interferon alone in the treatment of naïve patients with chronic hepatitis C and is well tolerated. However this combined treatment appears to be less effective than the association of pegylated IFN and ribavirin which represent the current standard treatment. Thus, the role of ketoprofen in the treatment of chronic hepatitis C needs to be further evaluated against such a treatment.

Adult↗
PubMed2002

Anti-hepatitis A virus seroprevalence and seroconversion in a cohort of patients with chronic viral hepatitis.

BACKGROUND: Patients with chronic hepatitis C infected by hepatitis A virus have a substantial risk of fulminant hepatitis or death, while the course of hepatitis A virus is uncomplicated in most subjects with chronic hepatitis B. AIM: To evaluate the prevalence of anti-hepatitis A virus antibodies and the incidence of hepatitis A virus seroconversion in a nationwide sample of 530 patients with chronic hepatitis B and/or hepatitis C infection initially susceptible to this infection after a follow-up of some years. RESULTS: The overall anti-hepatitis A virus prevalence was 85.7%, with no difference between males and females. By the age of 50 years, almost all patients were found to have been exposed to hepatitis A virus. After a mean follow-up period of 76 months the overall anti-hepatitis A virus seroconversion rate in the 76 initially susceptible individuals was 1.2 per 100 person/years. However, it was 0.3 per 100 person/years in those hepatitis B surface antigen positive but 3.36 per 100 person/years in those anti-hepatitis C virus positive. None of the seroconverters was affected by a clinically evident disease or showed deterioration of underlying chronic liver disease. CONCLUSIONS: The present study shows that Italian patients >50 years of age with chronic liver disease have already been exposed to hepatitis A virus suggesting that anti-hepatitis A virus screening is not advisable in these subjects.

Adolescent↗
PubMed2002

Retreatment with interferon plus ribavirin of chronic hepatitis C non-responders to interferon monotherapy: a meta-analysis of individual patient data.

BACKGROUND AND AIMS: Retreatment with a combination of alpha interferon (IFN) plus ribavirin of patients with chronic hepatitis C who did not respond to IFN monotherapy has not been assessed in large controlled studies. METHODS: To assess the effectiveness and tolerability of IFN/ribavirin retreatment of non-responders to IFN and to identify predictors of complete (biochemical and virological) sustained response, we performed a meta-analysis of individual data on 581 patients from 10 centres. Retreatment with various IFN schedules (mean total dose 544 mega units) and a fixed ribavirin dose (1000-1200 mg/daily depending on body weight) was given for 24-60 (mean 39.5) weeks. RESULTS: Biochemical end of treatment and sustained responses were observed in 271/581 (46.6%; 95% confidence interval (CI) 42.6-50.7%) and in 109/581 (18.7%; 95% CI 15.6-22.0%) cases, respectively. Two hundred and six of 532 patients (38.7%; 95% CI 34.6-42.9%) had an end of treatment complete response to retreatment while a complete sustained response occurred in 88 of 559 (15.7%; 95% CI 12.8-18.8%). Fifty four of 581 patients (9.2%; 95% CI 7.0-11.7%) stopped retreatment due to adverse effects. By logistic regression, complete sustained response was predicted independently by age <45 years (p=0.04), by normal pretreatment gamma-glutamyltransferase levels (p=0.01), and by a second course total IFN dose of at least 432 mega units (p=0.008). CONCLUSIONS: The overall low probability of effectiveness argues against indiscriminate retreatment of all IFN monotherapy non-responders with IFN/ribavirin. Patients less than 45 years old with normal gamma-glutamyltransferase levels who were retreated with high dose long course combination therapy had a complete sustained response rate of 30%.

Adult↗
PubMed2001

Vitamin E as treatment for chronic hepatitis B: results of a randomized controlled pilot trial.

BACKGROUND AND AIMS: Interferon-alpha treatment has been the treatment of choice for chronic hepatitis with unpredictable results. Recently, Lamivudine has been licensed for use against HBV infection with good results. Unfortunately, recurrence of viremia after lamivudine withdrawal is common and prolonged treatment can induce the emergence of resistant mutant strains. It has been shown that vitamin E can increase the host immune response, and this may provide protection against infectious diseases. METHODS: We evaluated vitamin E supplementation as therapy for chronic hepatitis B in a pilot study including 32 patients. Patients were randomly allocated to receive vitamin E at the dose of 300 mg twice daily for 3 months (15 patients) or no treatment (17 patients). They were seen monthly during the first 3 months and thereafter quarterly for additional 12 months. RESULTS: The two groups were comparable at enrollment. At the end of the study period, alanine aminotransferase (ALT) normalization was observed in 7 (47%) patients in vitamin E group and only in 1 (6%) of the controls (P=0.011); HBV-DNA negativization was observed in 8 (53%) patients in the vitamin E group as compared to 3 (18%) in the control group, respectively (P=0.039). A complete response (normal ALT and negative HBV-DNA) was obtained in 7 (47%) patients taking vitamin E and in none of the controls (P=0.0019). CONCLUSION: Vitamin E supplementation might be effective in the treatment of chronic hepatitis B.

Adult↗
PubMed2001

Interferon and prevention of hepatocellular carcinoma in viral cirrhosis: an evidence-based approach.

BACKGROUND/AIMS: To evaluate by meta-analysis of available literature whether interferon (IFN) reduces the incidence of hepatocellular carcinoma (HCC) in patients with hepatitis B virus (HBV) or hepatitis C virus (HCV)-related Child A cirrhosis. METHODS: Three randomized controlled trials and 15 nonrandomized controlled trials, including 4614 patients and comparing IFN to no treatment, were selected. Data on the incidence of HCC in IFN treated and untreated patients were extracted from each study. Meta-analysis by the DerSimonian and Laird risk difference (RD) method was used to pool observations. RESULTS: A different incidence of HCC between treated and untreated cirrhotic patients was observed for HCV (overall RD -12.8%; 95% CI -8.3 to -17.2%, P < 0.0001) and HBV (overall RD -6.4%; 95% CI -2.8 to -10%, P < 0.001). In HCV-related cirrhosis, the rate of HCC development was lower in sustained responders to IFN than in untreated patients (overall RD -19.1%; 95% CI -13.1 to -25.2%, P < 0.00001), with low heterogeneity among trials (P=0.053), and also in nonresponders vs. untreated patients (overall RD -11.8%; 95% CI -6.4 to -19.1%, P < 0.0001), although with significant heterogeneity. Inconsistency among the studies was a major problem, both for HCV (chi2 = 58.16 with 13 DF; P < 0.0001) and HBV (chi2 = 26.4 with 6 DF; P = 0.0001) related cirrhosis, and also when follow-up was shorter than 60 months. Consistent results were only observed when assessing data from European reports: in this subgroup no preventive effect of HCC was shown for HBV (overall RD -4.8%; 95% CI -11.1-1.5%, P, not significant), and only a weak effect for HCV (overall RD -10%; 95% CI -5.9 to -14.2%; P < 0.0001). CONCLUSIONS: Literature data pooling suggests a slight preventive effect of IFN on HCC development in patients with HCV-related cirrhosis. The magnitude of this effect is low and the observed benefit might be due to spurious associations. The preventive effect is more evident among sustained responders to IFN. IFN does not seem to affect the rate of HCC in HBV-related cirrhosis.

Antiviral Agents↗
PubMed2001

Interferon-alpha plus ribavirin and amantadine in patients with post-transplant hepatitis C: results of a pilot study.

BACKGROUND: Recurrence of hepatitis C after liver transplantation is almost constant and may lead to graft loss. The results of treatment with interferon and/or other agents have been controversial. AIMS: To evaluate the efficacy and safety of combination therapy with interferon-alpha2b (3 MU, 3 times weekly), ribavirin (600 mg daily) and amantadine (100 mg daily) in post-transplant hepatitis C. PATIENTS AND METHODS: Enrolled in the study were 9 liver transplant recipients with histologically proven recurrent hepatitis C. Patients were treated for 12 months and followed up for 6 months after treatment. RESULTS: Treatment was not tolerated: only one patient completed the planned course, two stopped therapy within the first 3 months and 6 needed a change. However, mean alanine aminotransferase levels significantly decreased during treatment and were significantly lower than baseline at the end of follow-up. One patient out of 9 (11%) achieved a biochemical and virological sustained response. Control liver biopsy showed improvement in 2/7 patients, no change in 3 and worsening in 2. CONCLUSIONS: In recurrent post-transplant hepatitis C, antiviral treatment with interferon, ribavirin and amantadine seems to be poorly tolerated. However further studies are needed before expressing any conclusion on this potentially important option.

Aged↗