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Biomedical subjects

S Fagiuoli

Publications and source records attributed to S Fagiuoli.

At least 19 recordsLinked to original sources
PubMed2006

Antiviral therapy for hepatitis C virus recurrence following liver transplantation: long-term results from a single center experience.

BACKGROUND: Hepatitis C virus (HCV) reinfection after liver transplantation is a virtually constant finding and leads to chronic hepatitis and cirrhosis in variable proportions. This study aimed to assess the safety and efficacy of alpha-interferon (IFN) plus ribavirin for recurrent HCV following liver transplantation. PATIENTS AND METHODS: Thirty of 55 patients (54.5%) with histologically proven HCV recurrence after liver transplantation were given antiviral therapy (alpha-IFN at a dose of 6 MU x 3 x week IM associated with oral ribavirin 1 g/d for 12 months) and followed up for a further 12 months after the end of the treatment. Liver and renal function tests, hemocytometric values, and HCV-RNA were assessed every 3 months throughout the therapy and follow-up. Liver biopsy was performed before and after the treatment and after another 12 months of follow-up. RESULTS: Eight patients (26.7%) were withdrawn from the treatment due to adverse events and another 8 (26.7%) needed a dosage reduction. Eleven patients (36.7%) had a biochemical and virological response, becoming aminotransferase and HCV-RNA negative at the end of the treatment; 6 patients (20%) still had a sustained response after 12 months of follow-up. All 6 patients are clinically stable at 6 years after completing the antiviral therapy. A low viral load before therapy was a positive predictor of sustained response. No histologically significant improvement was seen at the end of the therapy or after the follow-up. CONCLUSIONS: The combination of alpha-IFN plus ribavirin induced a sustained virologic response in 20% of liver transplant recipients with recurrent HCV, but intolerance of the therapy prompted its discontinuation or a dosage reduction in a large proportion of patients. However, we have observed a long-term efficacy of the antiviral therapy in the sustained responders.

Antiviral Agents↗
PubMed2005

Neuropsychological and neurophysiological evaluation in cirrhotic patients with minimal hepatic encephalopathy undergoing liver transplantation.

BACKGROUND: Cirrhotic patients without overt hepatic encephalopathy may have cerebral function alterations called minimal hepatic encephalopathy (MHE). Our goal was to evaluate the role of partial pressure of ammonia (pNH3), neuropsychological, and neurophysiological assessment in detecting cognitive changes in cirrhotic patients awaiting liver transplantation. MATERIALS AND METHODS: Fourteen cirrhotic patients listed for liver transplant were studied. All patients underwent the neuropsychological battery called PSE. Neurophysiological assessment including spectral EEG (sEEG), evoked potential P300 and pNH3 and venous and arterial ammonia levels was performed in all patients. Four patients were transplanted. RESULTS: Liver disease etiology was alcoholic in four patients, viral in six mixed in two, and cryptogenic in two. PSE scores revealed MHE in 8 patients; sEEG was altered in 6, and P300 in 1. No correlations were detected between P300, sEEG, and PSE. pNH3 and arterial ammonia levels were significantly higher in the subgroup of patients with altered sEEG and were correlated with theta band increase in sEEG but not with pathological PSE scores or P300 wave abnormalities. CONCLUSIONS: The combination of sEEG and PSE, and possibly also pNH3 and arterial ammonia, is useful in detecting cerebral function alterations in cirrhotic patients with no apparent encephalopathy, whereas P300 is not. The diagnosis of MHE obtained using the multimodal approach adopted in this study may enable the adequate treatment of these patients prior to surgery, which includes advising them not to drive and adjusting their priority on the waiting list for OLTx in the light of a condition that cannot be evaluated by Child Pugh score and MELD score.

Ammonia↗
PubMed2005

Comparison between nifedipine and carvedilol in the treatment of de novo arterial hypertension after liver transplantation: preliminary results of a controlled clinical trial.

There is no controlled clinical trial on the treatment of de novo arterial hypertension after liver transplantation (LT) a common complication using calcineurin inhibitors (CNI) for immunosuppressive therapy. The aim of this study was to compare the efficacy and safety of nifedipine, a calcium channel blocker, and carvedilol, an alpha1- and beta-blocker. The study included 50 patients who developed arterial hypertension after LT. The data on the first 30 patients who have completed 12-month follow-up are reported herein. Eighteen patients received nifedipine, and 12 patients received carvedilol. Patients were evaluated monthly at the outpatient clinic for 1 year. If patients developed severe adverse effects to nifedipine, they were switched to carvedilol and vice versa (therapy failure). The two groups were similar for clinical features, indications for LT, immunosuppressive therapy, and baseline blood pressures. A failure of treatment was observed in 9 of 18 patients treated with nifedipine (50.0%) and one of 12 patients treated with carvedilol (8%, P < .025). Nifedipine was effective in 4 of 18 patients, carvedilol, in 4 of 12 patients (22.21% vs 33.3%, P = NS). Two of the nine nonresponders to nifedipine responded to carvedilol. The efficacy of monotherapy was observed in 11 of 40 randomized patients (27.5%). Carvedilol monotherapy is as effective as nifedipine but far better tolerated.

Blood Pressure↗
PubMed2005

Tumour staging, morphology and p53 overexpression concur in predicting survival in hepatocellular carcinoma.

BACKGROUND/AIMS: The prognosis of hepatocellular carcinoma (HCC) on cirrhosis is hard to predict as it depends on tumour stage, underlying liver disease, type of treatment and, possibly, biological factors of the tumour itself. METHODS: We prospectively evaluated the survival of 91 consecutive patients with HCC on cirrhosis, diagnosed between January 1998 and December 1999. Clinical features and histological/biological aspects, including histotype, grade, p53 overexpression, cytoproliferation and apoptotic markers were analysed. RESULTS: Child-Pugh (P = 0.01), Okuda (P < 0.0001), Cancer of the Liver Italian Program (CLIP) staging (P < 0.0001) and type of treatment (P = 0.0001) were significantly related to survival. In the Cox model, CLIP staging was included as independent predictor of survival at step 1 (P < 0.0001) with Okuda at step 2 (P = 0.013). Amongst the biological factors, p53 overexpression and histotype were significantly related with survival (P = 0.0044 and 0.017 respectively). When clinical and biological variables were examined together in the Cox model, CLIP and Okuda were confirmed as being statistically related with survival (P < 0.0001 and =0.012) followed by histotype and p53 overexpression (P = 0.019 and 0.02). CONCLUSIONS: CLIP, Okuda, histotype and p53 overexpression are the strongest predictors of survival in this series of patients. These data confirm that staging of the tumour and underlying liver disease are strictly related to prognosis but support the concurrent role of clinical and biological factors in upgrading our capacity of predicting the fate of HCC patients.

Aged↗
PubMed2002

Liver transplantation: the Italian experience.

BACKGROUND: Liver transplantation is the standard treatment for patients with end-stage liver disease no longer responsive to conventional medical treatment AIMS: To report the long-term experience of liver transplantation in Italy. PATIENTS AND METHODS: Data were obtained retrospectively by means of a multiple-item form collected from 15 Italian liver transplant centres. The filing centre was centralized. RESULTS: A total of 3323 liver transplants were performed on 3026 patients, with a cumulative proportional survival of 72.4%. Three, 5 and 10 years' patient survival rates were 72.3%, 68.8% and 61.3%, respectively. The most common indication for liver transplantation were hepatitis B virus (+/- hepatitis D virus)- and hepatitis C virus-related cirrhosis (59.4%). Excellent survival rates were observed particularly in controversial indications, such as alcoholic cirrhosis, hepatitis B virus-related cirrhosis and hepatocellular carcinoma. Retransplantation was required in 8.9% of the cases. The overall prevalence of acute cellular rejection episodes was 43.5%. In our study population, primary non-function and disease recurrence were the most common causes of graft failure (28.7% and 25.4%, respectively). Infections and/or sepsis were the most common causes of death after transplantation (42%). CONCLUSION: This study confirms that patients with controversial indications to liver transplantation such as alcoholic cirrhosis, HBV-related cirrhosis and hepatocellular carcinoma can achieve excellent survival when properly selected.

Adolescent↗
PubMed2002

The Italian experience on paediatric liver transplantation: 1988-1999 report.

BACKGROUND: Liver transplantation is the treatment of choice for end-stage liver disease in both adult and paediatric patients. The Italian experience in paediatric liver transplantation during the period 1988-1999 is reported herein. PATIENTS AND METHODS: This report concerns 228 liver transplantations performed in 207 patients (100 male, 107 female, mean age 5.1+/-4.4 years) in 11 Italian centres. The mean waiting time on the transplantation list was 6.1+/-8.9 months and the main indications for the procedure were biliary atresia, inborn metabolic disorders, liver cirrhosis, liver neoplasms, Alagille syndrome, and fulminant hepatic failure. RESULTS: The cumulative survival rate was 77%, 76%, 73%, and 71% at 1, 3, 5, and 7 years. The overall prevalence of acute rejection was 54%. Survival was significantly affected by re-transplantation (p=0.0002), by United Network for Organ Sharing 4 status at transplantation (p=0.016), and, among the indications for the procedure, by fulminant hepatic failure (p=0.004). Fifty patients (24%) died during the observation period. The main causes of death were primary non-function of the graft and sepsis CONCLUSIONS: This study shows that liver transplantation in paediatric age, in Italy, is an effective procedure providing a 5-year survival rate comparable to that attained in the largest published series.

Cause of Death↗
PubMed2002

Histology predicts cirrhotic evolution of post transplant hepatitis C.

BACKGROUND: Hepatitis C recurring after orthotopic liver transplantation varies in severity and some patients rapidly develop fully established liver cirrhosis. Neither clinical nor biological markers of such rapid cirrhotic evolution are available. AIM: To assess the value of histology in identifying patients who will develop cirrhosis shortly after liver transplantation. PATIENTS AND METHODS: Only cases of recurrent hepatitis C diagnosed by both hepatitis C virus-RNA positive serum and liver changes consistent with hepatitis, with no other causes of allograft injury, were considered. A total of 128 liver biopsies were scored from 29 consecutive patients with a mean follow up of 48 (13.97) months. The histological activity index was evaluated according to Ishak et al. The time of the first histological diagnosis of recurrent hepatitis C in the absence of rejection was defined as time of histological recurrence (RHC-T). RESULTS: First histological diagnosis of recurrent hepatitis with no features of rejection was obtained at the six month biopsy in 23 of 29 cases. By the end of follow up, nine patients had developed cirrhosis (mean follow up 38 (14.39) months (range 18-60)). The remainder (mean follow up 46 (13.40) months (24-72)) showed a spectrum of fibrosis but no cirrhosis. Severe necroinflammatory lesions at RHC-T significantly correlated with rapid development of cirrhosis. At the RHC-T biopsy, only cases evolving into cirrhosis showed confluent necrosis. The median value of the histological activity index was 11 (mean 11.11 (1.76) (range 9-14)) in patients who developed cirrhosis and four (mean 4 (1.78) (range 1-8)) in the others (p<0.0001). A histological activity index > or =9 was associated with rapid development of cirrhosis in 100% of cases. CONCLUSIONS: After liver transplantation, the histological activity of recurrent hepatitis C predicts the risk of development of cirrhosis. By adopting Ishak's scoring system, a histological activity index > or =9 was 100% sensitive/specific in identifying subjects who rapidly developed cirrhosis.

Acute Disease↗
PubMed2001

Bone metabolism and gonad function in male patients undergoing liver transplantation: a two-year longitudinal study.

Osteodystrophy is a major complication of end-stage liver disease, especially in postmenopausal women. Our aim in this study was to evaluate bone metabolism and gonad function in men undergoing orthotopic liver transplantation (OLTx). Twenty-three consecutive men (mean age 48+/-13 years) evaluated for OLTx were studied, assessing the following parameters at baseline and 3, 6, 12 and 24 months after OLTx: lumbar spine (L2-L4) bone mineral density (BMD), parathyroid hormone (PTH), osteocalcin (BGP), 25-hydroxyvitamin D (25OHD), free testosterone (FT) and gonadotropins (FSH, LH). At baseline, 12 patients (52%) had a T-score <-2.5 SD and the mean BMD was 0.806+/-0.11 g/cm2 (range 0.470-1.045 g/cm2). The BMD was lower 3 months after OLTx and significantly higher 12 and 24 months after OLTx. A significant increase in serum BGP was observed at 6, 12 (p<0.05) and 24 months (p<0.005) after OLTx. The mean serum PTH level was 26.6+/-3.1 pg/ml at baseline and increased significantly at 12 and 24 months (to 49.4+/-9.9 and 61.2+/-10.1 pg/ml, respectively; p<0.05). 25OHD serum levels were low at baseline and returned to the normal range after 12 and 24 months (baseline, 8.73+/-1.54 ng/ ml; 12 months, 16.4+/-2.6 ng/ml; 24 months, 17.67+/-3.1 ng/ml; p<0.05). FT was significantly lower at baseline than in a group of 10 healthy controls (5.09+/-10.99. vs 10.3+/-1.1 pg/ml; p<0.0001). After OLTx a significant increase in FT was recorded at 6, (p<0.05) and 24 months (p<0.005). FT was not correlated with BMD, however. After OLTx an increase in FSH and LH was observed (but failed to reach statistical significance) at 3 and 6 months, followed by a slight reduction at 12 and 24 months. Thus a high proportion of men with end-stage liver disease do have osteoporosis. After OLTx, an early recovery of gonad function is observed, followed by an increase in bone mass, which occurs from the sixth month onward.

Adult↗
PubMed2001

Histological features after liver transplantation in alcoholic cirrhotics.

BACKGROUND/AIMS: Though alcoholic cirrhosis is a common indication for liver transplantation, it carries the risk of alcohol recidivism and consequent graft failure. This study aims to evaluate the effect of alcohol recidivism on survival rates and histological parameters in patients transplanted for alcoholic cirrhosis, with and without hepatitis C virus (HCV) infection. METHODS: Fifty-one out of 189 consecutive transplanted patients underwent psychosocial evaluation and liver biopsy at 6 and 12 months, then yearly after transplantation. RESULTS: The cumulative 84 month survival rate was identical in patients transplanted for alcoholic (51%) and non-alcoholic cirrhosis (52%). No difference emerged between anti-HCV negative vs. positive alcoholic cirrhosis patients. Psycho-social evaluation revealed alcohol recidivism in 11/34 long-term survivors, but this did not affect overall survival rate in patients with or without HCV. In anti-HCV negative cases, fatty changes and pericellular fibrosis were significantly more common in heavy drinkers than in occasional drinkers and abstainers. When HCV status was considered regardless of alcohol intake, fibrosis was significantly more frequent in patients with HCV. CONCLUSION: Alcohol recidivism after transplantation in alcoholic cirrhosis patients does not affect survival, irrespective of HCV status. Fatty changes and pericellular fibrosis are the most relevant histological signs of heavy alcohol intake.

Adult↗
PubMed2001

HBV and HCV infections in heart transplant recipients.

BACKGROUND: Heart transplant (HTx) recipients risk acquiring hepatotropic viral infections such as hepatitis B virus (HBV) and hepatitis C virus (HCV), and the impact of these infections on post-HTx survival remains unclear. The aim of the present study was to define the prevalence, clinical features, and natural history of HBV and HCV infections in a cohort of HTx recipients. METHODS: We retrospectively studied 360 consecutive patients who had undergone HTx. Clinical picture, hepatic injury indexes, and HBV/HCV viral serology were followed post-transplant. RESULTS: During follow-up (average, 8 +/- 3.1 years), 49 (16.5%) of the HTx recipients tested positive for at least 1 of the 2 viruses (3.1% HBV, 12% HCV, 0.5% concomitant infection). The prevalence of HCV infection in heart transplant recipients transplanted before and after 1990 was 28% and 4.2%, respectively, the latter being markedly lower (p < 0.001) than in earlier series of HTx recipients and much lower than expected in the age- and sex-matched general population. All HBV-positive and 58% of HCV-positive recipients developed chronic liver disease. Sixteen percent of patients developed cirrhosis during follow-up, and 8% died of end-stage liver disease. CONCLUSIONS: The prevalence of HBV and HCV in a large population of HTx recipients is not very different from that reported in the general population. Active viral replication of HBV and an aggressive natural history of both infections are seen in HTx recipients, however. The low prevalence of HBV- and HCV-related infection in recent series probably reflects current viral screening and vaccination policies.

Adult↗
PubMed2001

Does the choice of treatment influence survival of patients with small hepatocellular carcinoma in compensated cirrhosis?

OBJECTIVE: Untreated patients with small, single hepatocellular carcinoma (HCC) in compensated cirrhosis are characterized by a relatively good prognosis. METHODS: We report the findings generated in a retrospective study on a cohort of 186 consecutive patients with small (< 5 cm) HCC in Child A or B cirrhosis, who were transplanted (four), underwent surgery (15), or were treated with percutaneous ethanol injection (117), lipiodol chemoembolization (44) or best supportive care (six), depending on their clinical features. RESULTS: Overall survival was 26% at 5 years (31% Child A, 20% Child B), with a mean and median survival of 44 and 38 months, respectively. The longest survival was obtained with transplantation and surgery, and the worst with best supportive care. When untreated patients were not considered, no significant differences were observed between the different types of treatment, however, even when patients in the Child A group were considered alone. Almost all the patients who underwent surgery relapsed. No significant difference was observed in relation to the stage of the disease, while alpha-fetoprotein levels were singled out as the only relevant prognostic factor in a multivariate Cox's regression model. Costs per year of life saved were extremely high for transplantation and lowest for ethanol injection, with surgery being less expensive than chemoembolization. CONCLUSIONS: This study confirms that patients with single, small HCC nodules in well compensated cirrhosis should be treated. The choice of type of treatment should be based on the availability of local resources and expertise, and on the patients' preference, after they have been properly informed on the survival, morbidity and mortality related to each treatment option. The relative cost of the procedures should also be considered.

Adult↗
PubMed2000

Long-term medical and psycho-social evaluation of patients undergoing orthotopic liver transplantation for alcoholic liver disease.

The major concern in transplanting patients with alcoholic liver disease (ALD) is the high rate of alcohol recidivism. Our aim was to assess the long-term outcome of liver transplantation (OLT) in a group of ALD patients in terms of post-OLT alcohol recidivism and its relationship with pre-OLT psychosocial variables and medical follow up. Fifty-one ALD patients underwent strict medical and psychosocial evaluation before and after OLT. Alcohol abuse was recorded in 60% and alcohol dependence in 40% of patients before OLT. The 5-year survival was similar to the one observed in non-ALD transplanted patients (64 vs 56%). Alcohol recidivism was observed in 33% of transplanted patients, 64% of whom were occasional and 36% were heavy drinkers. The admission of alcoholism by the patient and his/her family prior to OLT significantly predicted abstinence after OLT. A multidisciplinary approach evaluating medical and psycho-social variables before OLT and a close follow up after OLT are mandatory for ALD patients.

Alcoholism↗
PubMed2000

Lymphoproliferative disorders in heart transplant recipients: role of hepatitis C virus (HCV) and Epstein-Barr virus (EBV) infection.

Post-transplant lymphoproliferative disorders (PTLD) are a well known complication after orthotopic heart transplantation (OHT). Although Epstein-Barr virus (EBV) infection has long been implicated in the pathogenesis of such disorders, other factors may play a part. Because of its lymphotropic properties, hepatitis C virus (HCV) may induce clonal expansion of B-lymphocytes and lead to PTLD. The aim of this study was to evaluate the potential association between HCV and EBV infection and PTLD in OHT patients. The retrospective study considered 404 adult patients screened for HCV. EBV serology, histology, and molecular analysis on tissue biopsies were performed in the PTLD patients (10/404, 2.5%). HCV positivity was found in 36/404 (8.9%) patients. The EBV genome was expressed on all neoplastic tissue samples analyzed. A higher proportion of HCV-positive patients developed PTLD than the HCV-negative cases (8% vs 2%, P = 0.017). EBV has a demonstrated role in the onset of PTLD, but HCV infection probably has to be considered as well.

Adolescent↗
PubMed1998

Bone metabolism in orthotopic liver transplantation: a prospective study.

Bone mineral density (BMD) and mineral metabolism were assessed in 54 patients with end-stage liver disease who were evaluated for orthotopic liver transplantation (OLT) and assessed 3, 6, and 12 months after surgery in 26 patients who underwent OLT. Serum and urinary electrolyte and mineral levels, serum liver function test results, and parathyroid hormone (PTH), osteocalcin (BGP), 25-hydroxyvitamin D, and urinary hydroxyproline levels were assessed. BMD of the lumbar spine was measured at baseline and 3, 6, and 12 months after OLT. At baseline, 40.7% of patients had BMD below the fracture threshold (0.800 g/cm2). Using multiple stepwise regression analysis, we found that BMD was significantly (P < .0001) affected by age, serum creatinine level, and PTH level but not by indices of cholestasis or liver function. In the patients who underwent OLT, a 1.4% reduction (P < .006) was observed in BMD 3 months after OLT. Thereafter, BMD returned to pretransplant values. A significant increase in serum BGP was observed after 6 (P < .02) and 12 (P < . 005) months. PTH levels increased progressively 3 (P < .02), 6 (P < . 001), and 12 (P < .0001) months after OLT. This increase did not seem to be caused by cyclosporine-induced nephropathy. It was concluded that osteopenia is a major complication in hepatic cirrhosis, regardless of its causes. The increase in serum BGP levels 6 and 12 months after OLT indicates metabolic activation of osteoblasts. The increase in PTH levels after OLT warrants further investigation.

Absorptiometry, Photon↗
PubMed1998

Hepatitis C status of heart transplant recipients.

The records of 155 consecutive patients who underwent successful heart transplantation (HTx) were reviewed to document the incidence of hepatitis C (HCV) infection. One patient was HCV RNA positive pre-HTx, and 12 patients (8%) developed transient or permanent HCV positivity post-HTx. HCV RNA positivity was associated with biochemical features of liver injury. Liver biopsy was performed in 8, and demonstrated features of chronic hepatitis in all. Two patients died of chronic liver failure at 50 and 56 months post-HTx, respectively. Interferon therapy was given to three patients, two of whom converted to HCV negativity. This study suggests that HCV infection is more common than previously anticipated in HTx patients, and varies from a mild transient condition to a fatal chronic liver failure.

Adolescent↗
PubMed1996

Association between reactive oxygen species and disease activity in chronic hepatitis C.

Reactive Oxygen Species (ROS) may be involved in the damage occurring in the course of chronic HCV infection. Individuals with chronic hepatitis C present increased hepatic levels of malondialdehyde (MDA) and reduced levels of glutathione. To determine whether these observations are associated with serological evidence for ROS injury, MDA and protein carbonyl content (PCC) of serum was determined in 20 HCV positive patients (14 chronic active hepatitis -- CAH and 6 cirrhosis) and 20 controls. Compared to controls, HCV positive subjects had increased levels of MDA (13.33 +/- 0.21 SE ng/ml vs. 9.90 +/- 0.65 P < .05) and PCC (4.74 +/- 0.21 mmol/mg vs 3.68 +/- 0.21, p < .02). Patients with CAH had higher levels than did cirrhotics. Both MDA and PCC correlated with serum ALT levels (r = .792 and r = .818 respectively, p < .001). A common origin for MDA and PCC found in patients with chronic hepatitis C was suggested by the correlation between the two measures (r = .741, p < .001). No correlation were found between MDA or PCC and the hepatic iron content. These data demonstrate that: (1) lipid and protein oxidation occur in chronic hepatitis C, (2) oxidative damage can be demonstrated as increased serum levels of MDA and PCC, and (3) both MDA and PCC levels correlate with disease activity.

Adult↗