Surveillance of hospitalised patients with influenza-like illness during pandemic influenza A(H1N1) season in Sicily, April 2009-December 2010.

This paper describes the epidemiology of hospitalised cases with influenza-like illness (ILI) and laboratory-confirmed influenza A cases in Sicily (Italy) during the 2009 influenza pandemic. The first ILI case diagnosed as infected with pandemic influenza A(H1N1)2009 in Sicily was reported in June 2009 and it rapidly became the dominant circulating strain. In the period from 30 April 2009 through 31 December 2010, a total of 2,636 people in Sicily were hospitalised for ILI and 1,193 were laboratory-confirmed for influenza A. Basic demographic and clinical information for all hospitalised patients was collected and population mortality rates (PMRs) and case fatality ratios (CFRs) were calculated. The median age of hospitalised patients infected with pandemic influenza A(H1N1)2009 was significantly lower than that of hospitalised ILI cases in general (18.0 vs. 32.1 years; p<0.0001). Among adults, women were more susceptible than men. The majority of clinical presentations were mild, but 6.6% of hospitalised patients required admission to an intensive care unit, of whom 26.3% had confirmed influenza A. Twenty-four fatal cases were documented. The age group of 45­54 year-olds showed the highest PMRs once hospitalised, while CFRs were higher in elderly patients of 65 years and older. All fatal cases were confirmed as influenza A(H1N1)2009 and most of them had established risk factors for influenza complications.

Clinical burden of screening asymptomatic patients for coronary artery disease prior to liver transplantation.

The aim of this study is to assess the clinical burden of silent coronary artery disease (CAD) in cirrhotic candidates for liver transplantation (LT), and to evaluate the usefulness of a CAD screening approach. Between July 1999 and January 2006, we evaluated 627 LT candidates. All of them underwent a detailed clinical history. Sixteen had a previous diagnosis of CAD or symptoms suggestive (2.5%). The remaining 611 underwent further tests according to a predefined protocol, including EKG, echocardiogram and, on the basis of CAD risk factors, heart stress tests. Selective coronary angiography (SCA) was performed in the 30 patients with positive heart stress test: in only 2 did SCA show any CAD, and in both it was subcritical disease requiring neither intervention nor contraindicating LT. The 611 screened patients continued their follow-up until study closure or death. No coronary events occurred in the study population in a mean follow-up of 32.50 months (+/- 23.67 DS). No perioperative mortality related to CAD occurred in the 233 transplanted patients. In conclusion, no prognostic advantage was achieved by following a strict CAD screening protocol, leading us to believe that the cost-effectiveness of a similar screening can be unacceptably high in our setting.

A safe immunosuppressive protocol in adult-to-adult living related liver transplantation.

BACKGROUND: In this series of 32 adult-to-adult living related liver transplantations, we assessed the efficacy and safety of basiliximab in combination with a tacrolimus-based regimen. Basiliximab, a chimeric monoclonal antibody directed against the alpha chain of the interleukin-2 (IL-2) receptor (CD25), has been extensively evaluated as induction therapy for cadaveric liver transplant recipients. PATIENTS AND METHODS: Thirty-two adult-to-adult living related liver transplantations were performed in the last 3 years. All patients received two 20 mg doses of basiliximab (days 0 and 4 posttransplantation) followed by tacrolimus (0.15 mg/kg/d; 10-15 ng/mL target trough levels) and steroids (starting with 20 mg IV switched to PO as soon as the patient was able to eat and weaned within 1-2 months). The average follow-up was 395 days after transplantation. RESULTS: Of the patients, 93.75% remained rejection-free during follow-up with an actuarial rejection-free probability of 92.59% within 3 months. Two patients (6%) had one episode of biopsy-proven acute cellular rejection (ACR). Actuarial patient and graft survival rates at 3 years were 86.85% and 81.25%. One patient (3%) experienced one episode of sepsis. There was no evidence of cytomegalovirus infections or side effects related to the basiliximab. We found zero de novo malignancy but we observed two patients with metastatic spread of their primary malignancy during the follow-up. CONCLUSION: Basiliximab in association with tacrolimus and steroids is effective as prophylaxis of ACR among adult living related liver transplant recipients.

Acceptance of marginal liver donors increases the volume of liver transplant: early results of a single-center experience.

To expand the donor pool, clinicians are continually modifying criteria to accept organs, particularly those in the so-called expanded or marginal donor pool. The concept and definition of a marginal donors continues to evolve. The impact of their use is the result of a combination of donor and recipient factors. Most clinicians accept steatosis above 30%, donor age over 60 years, prolonged ischemia time, prolonged intensive care unit stay, hypernatremia, previous cardiac arrest, prolonged episodes of hypotension, large use of inotrope drugs, and elevated liver function tests as criteria for designation of a marginal organ. In June 2003, we started to use marginal donors each year tripling the number of transplants per year at our center.

Functional, life-threatening disorders and splenectomy following liver transplantation.

UNLABELLED: Splenectomy (SPL) in cirrhotic patients undergoing liver transplantation (LTx) may resolve specific problems related to the procedure itself, in case of functional and life-threatening clinical situations often occurring as a result of liver cirrhosis and portal hypertension. METHOD: A single-center experience of ten splenectomies in a series of 180 consecutive adult liver transplant patients over a period of 6 yr is reported. The mean patient age was 46.8 +/- 9.5 yr (range 25 57 yr). Indications for SPL were post-operative massive ascitic fluid loss (n = 3), severe thrombocytopenia (n = 3), acute intra-abdominal hemorrhage (n = 2), infarction of the spleen (n = 1), and multiple splenic artery aneurysms (n = 1). RESULTS: Extreme ascites production due to functional graft congestion disappeared post-SPL, with an improvement of the hepatic and renal functions. SPL was also effective in cases of thrombocytopenia persistence post-LTx, leading to an increase in the platelet count after about 1 wk. Bleeding episodes related to left-sided portal hypertension or trauma were also resolved. The rejection rate during hospitalization was 0%, and no other episodes were recorded in the course of the long-term follow-up. However, sepsis with a fatal outcome occurred in 4 patients, i.e. between 2 and 3 wk post-SPL in three cases and 1 yr after the procedure as a result of pneumococcal infection in the last case. Fatal traumatic cranial injury occurred 3 yr post-LTx in another case. Five patients (50%) are still alive and asymptomatic after a median follow-up period of 36 months. CONCLUSION: The lowering of the portal flow appears to resolve unexplained post-operative ascitic fluid loss as a result of functional graft congestion following LTx. However, because of the enhanced risk of SPL-related sepsis, a partial splenic embolization (PSE) or a spleno-renal shunt could be used as an alternative procedure because it allows us to preserve the immunological function of the spleen. SPL is indicated in case of post-transplant bleeding due to left-sided portal hypertension and trauma, spleen infarction, and to enable prevention of hemorrhage in liver transplant patients with multiple splenic artery aneurysms. Severe and persistent thrombocytopenia could be treated with PSE. Because the occurrence of fatal sepsis post-SPL is a major complication in LTx, functional disorders, such as ascites and thrombocytopenia, should be treated with a more conservative approach.

Further evidence for an association between non-insulin-dependent diabetes mellitus and chronic hepatitis C virus infection.

Non-insulin-dependent diabetes mellitus (NIDDM) may be associated with chronic hepatitis C virus (HCV) infection. This was studied further in two parts. First, 1,151 patients with HCV-related cirrhosis and 181 patients with hepatitis B virus (HBV)-related cirrhosis, well matched for age, sex, and severity of cirrhosis, were reviewed retrospectively. The prevalence of diabetes mellitus was higher in HCV-related cirrhosis (23.6%) than in HBV-related cirrhosis (9.4%; odds ratio [OR], 2.78; 95% confidence interval [CI], 1.6-4.79; P =.0002). The prevalence of diabetes mellitus was associated closely with the Child-Pugh score (OR, 3.83; 95% CI, 2. 38-6.17; P <.0001) and increasing age (OR, 1.02; 95% CI, 1.00-1.03; P =.0117). Second, 235 patients with biopsy confirmed chronic HBV or HCV underwent an oral glucose tolerance test. Only 1 of 70 patients with chronic viral hepatitis without cirrhosis was diabetic. However, 31 of 127 patients with HCV-related cirrhosis (24.4%) were diabetic compared with 3 of 38 patients with HBV-related cirrhosis (7.9%, P =.0477). The major variables associated with NIDDM were cirrhosis (OR, 14.39; 95% CI, 1.91-108; P =.0096) and male sex (OR, 4.64; 95% CI, 1. 32-16.18; P =.0161). Fasting insulin levels in 30 patients with HCV-related cirrhosis and diabetes mellitus were elevated significantly, which was consistent with insulin resistance. However, acute insulin responsiveness was reduced in all patients with HCV infection and diabetes suggesting concomitant B-cell dysfunction. This study confirms an association between HCV and NIDDM.

Hepatic sickling: an unusual cause of liver allograft dysfunction.

Orthotopic liver transplantation can be performed successfully in thalassemia. In this article, we describe a case of liver transplantation in a patient with sickle cell/beta-thalassemia complicated by liver sickling. Intrahepatic sickling must be considered in case of allograft dysfunction. This condition can easily be diagnosed by biochemical investigation and liver ultrasonography.

[Method of functional impression in prosthetic treatment with distal extension with dental-mucosal support]. / Metodica d'impronta funzionale nella protesi dentaria ad estensione distale con appoggio dento-mucoso.

Having examined the biomechanical problems regarding free-end tooth-tissue borne dentures caused by the different resilience of denture support structures and changes in the resilience of fibre-mucosa, and having reviewed the impression methods now in use, the authors describe a functional impression method used to obtain a clinical and instrumental record of the individual conditioning of fibre-mucosa support by functional occlusal stress. The aim was to reduce the resilience of fibre-mucosa to levels comparable to periodontal and articular levels. The purpose was to achieve an optimal functional morphology of the prosthetic occlusal surface in order to guarantee the static and dynamic equilibrium of the denture. The authors describe a protocol based on weekly relining sessions and clinical and instrumental controls performed at every other session until optimal results have been obtained. Instrumental tests were carried out using the computerised occlusal analyser: T-SCAN version II. The authors used this device to measure the redistribution of occlusal forces acting on the occlusal surface in an antero-posterior and latero-lateral direction in subsequent sessions and the corresponding position of the centre of forces in the central area. In line with the results of earlier studies carried out by other researchers, the authors confirm that when maximum conditioning of the fibre-mucosa support is achieved, it only retains a slight residual elasticity.

Recurrent postinfantile syncytial giant cell hepatitis after orthotopic liver transplantation.

Syncytial giant cell hepatitis is a severe form of hepatitis characterized by diffuse giant cell transformation of hepatocytes. The disease may evolve to chronic cholestatic cirrhosis necessitating liver transplantation. We report the case of an adult liver transplant recipient presenting with early recurrent disease without concomitant clinicobiochemical syndrome. Early recurrence of giant cell hepatitis after liver transplantation favors the hypothesis of a transmissible agent as the etiology of the disease. Routine follow-up liver biopsy is necessary in these cases in order to gain more information about the precise incidence and aggressivity of disease recurrence in the allograft.

Pilot study of the combination of interferon alfa and ribavirin as therapy of recurrent hepatitis C after liver transplantation.

Recurrent hepatitis C virus (HCV) in liver transplant patients is a major cause of graft loss, liver failure, and need for retransplantation. The results available to date with the use of interferon alfa (IFN-alpha) in the treatment of recurrent HCV in liver transplant patients have been disappointing. The aim of this study was to evaluate the efficacy and clinical utility of post-transplant combination therapy with IFNalpha2b (3 million units 3 times weekly) and oral ribavirin (1,200 mg/d) for a duration of 6 months, followed by maintenance with ribavirin alone for an additional 6 months. Twenty-one liver transplant recipients with recurrent hepatitis C infection (HCV-RNA-positive; active hepatitis without rejection on biopsy) were enrolled in this study. Pretreatment serum alanine transaminase (ALT) levels were at least two times the upper limit of normal. Before treatment, all patients were HCV-RNA-positive and mean HCV-RNA titers were 125 million genome-equivalents/mL. Mean pretreatment histological score was 6.3 +/- 2. After 6 months of combination therapy, all 21 patients had normal ALTs. Ten patients (48%) cleared HCV-RNA from their serum, as assessed by polymerase chain reaction (PCR), and HCV-RNA levels decreased significantly in the others (P = .0001). Improvement in histological score was seen in all patients after combination therapy (P = .0013). During maintenance ribavirin monotherapy, ALT remained normal in all but 1 of the 18 patients who tolerated therapy. HCV-RNA reappeared in 5 patients, but HCV-RNA levels did not return to pretreatment levels (P = .0004). Comparison of pretreatment and postribavirin monotherapy liver biopsies revealed improvement in all but 1 of the 18 patients who tolerated ribavirin (P = .0002). Side effects were restricted to anemia, which necessitated cessation of ribavirin therapy in 3 patients. No patient experienced graft rejection during the study period. These results are significantly better than those reported with IFN-alpha monotherapy. Most importantly, there was a complete absence of graft rejection. These results suggest that the combination of IFN-alpha and ribavirin is effective in reducing HCV-RNA levels and ameliorating hepatocellular injury in recurrent HCV after liver transplantation, and that maintenance therapy with ribavirin monotherapy can maintain the biochemical and histological response.

Serum hepatitis C virus (HCV)-RNA and response to alpha-interferon in anti-HCV positive chronic hepatitis.

Hepatitis C virus (HCV) replication was assessed before and during alpha-interferon (IFN) treatment in 22 anti-HCV positive patients with posttransfusion or sporadic chronic hepatitis (CH). Eleven patients were "responders" and 11 patients "non-responders" to IFN. Thirteen anti-HCV negative healthy subjects and five anti-HCV negative patients with autoimmune CH served as controls. Serum HCV-RNA was detected by the polymerase chain reaction (PCR) in all untreated anti-HCV positive patients but in none of the anti-HCV negative subjects. PCR primers from the 5'-noncoding (NC) region were more sensitive than primers from a non-structural (NS5) region in detecting HCV-RNA (21/22, 95% vs. 7/22, 32%, respectively). Positive strand HCV-RNA titre and positivity rate for the negative strand were similar in responders and non-responders before IFN treatment, as well as anti-c100-3 titre by enzyme-linked immunosorbent assay (ELISA), and anti-5-1-1, anti-c33c, anti-c22 positivity rate by immunoblot assay (RIBA). HCV-RNA positivity by both NC and NS primers was more frequent before IFN among responders. During IFN treatment, serum HCV-RNA was detectable, mostly at low titres, in 1 (NC positive) of the 11 responders and in 9 (4 NS positive and 5 NC positive) of the 11 non-responders. Among the four non-responders who were NS positive during IFN, three were NC positive before IFN. Serum HCV-RNA was always found in our post-transfusion or sporadic anti-HCV positive patients with CH. Viraemia generally decreased during IFN treatment, but no available HCV markers clearly distinguished responders from non-responders before IFN treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

A performance evaluation of the expert system 'Jaundice' in comparison with that of three hepatologists.

The diagnostic performance of an Expert System (Jaundice) designed to discriminate between different causes of jaundice was evaluated in a test sample of 200 consecutive in-patients with serum bilirubin greater than or equal to 51 mumol/l. The average probability assigned to true diagnosis, the non-error rate and the overall accuracy were, respectively, 55%, 77% and 70%. The Expert System's discriminatory ability in probabilistic prediction, assessed by a method based on continuous functions of the diagnostic probabilities (Brier score) was good. We also compared the ability of our Expert System to that of three experienced hepatologists, who were required to give a diagnosis in 20 cases following the same protocol used by computer (i.e., by asking only clinical and laboratory items). Both the hepatologists and Jaundice achieved a correct diagnosis in 70% of 20 cases, but the Expert System asked a significantly higher average number of questions during each consultation. Analysis of the reasoning pathway made by an external referee showed a high agreement between the diagnostic strategies of the Expert System and the physicians. We conclude that Jaundice can be a useful tool to support a physician with insufficient clinical experience in this field to generate correct diagnostic hypotheses.

Hepatitis C virus replication in 'autoimmune' chronic hepatitis.

Both high and low anti-hepatitis C virus antibody (anti-HCV) prevalence has been reported in autoimmune chronic active hepatitis. Therefore, we studied 15 consecutive HBsAg-negative, ELISA anti-HCV-positive, autoantibody-positive patients with biopsy proven chronic active hepatitis in order to confirm ELISA specificity by immunoblot test (RIBA-HCV), and to evaluate HCV replication by serum HCV-RNA. Nine patients were anti-nuclear, three type 1 anti-liver-kidney microsomal and three anti-smooth muscle antibody positive. None had associated autoimmune disease. All cases showed mild clinical disease and only moderate necroinflammatory activity. Response to prednisone was poor. RIBA-HCV confirmed ELISA results in all patients. HCV-RNA was found in the serum from 10 patients. Institution of alpha-interferon treatment in three steroid non-responsive patients was followed by prompt normalization of transaminases. Thus, a subgroup of autoantibody-positive chronic active hepatitis can be recognized as HCV-related and should be clinically and etiologically distinguished from autoimmune chronic active hepatitis. Trials of alpha-interferon treatment are worthwhile in this condition.

Is autoimmune chronic active hepatitis a HCV-related disease?

We evaluated the specificity and clinical relevance of anti-hepatitis C virus antibody positivity in 22 HBsAg-negative patients with autoimmune (anti-nuclear, anti-actin or anti-liver-kidney microsomal antibody positive) chronic active hepatitis. An ELISA anti-HCV test and a recombinant immunoblot assay (RIBA-HCV) were used. Thirteen patients (59%) were anti-HCV positive and five (23%) anti-HCV negative by both ELISA and RIBA-HCV tests. Four patients (18%) were borderline positive by ELISA (OD less than 1.0), and three of them (all with severe disease) were negative by RIBA. Histologic necroinflammation, AST/ALT and gamma-globulins levels were higher and response to prednisolone treatment was better in RIBA anti-HCV-negative than in anti-HCV-positive cases. We confirmed with both RIBA and ELISA tests the high prevalence of anti-HCV already reported by ELISA in anti-nuclear and anti-liver-kidney microsomal antibody positive chronic active hepatitis. False positive for anti-HCV (i.e., a positive ELISA test not confirmed by RIBA) occurred only among patients with severe disease. Since RIBA-negative subjects showed the best response to corticosteroid, they might represent the only subset of cases of 'true' autoimmune chronic active hepatitis.

Hepatitis C virus antibodies in chronic liver diseases of different aetiology.

To define the prevalence of Hepatitis C Virus (HCV) infection in patients with chronic hepatitis or cirrhosis of any aetiology, we tested a group of 372 consecutive subjects with biopsy-proven chronic liver disease (CLD) for anti-HCV antibodies, excluding active drug-addicts and alcoholics. Our results show that in Southern Italy HCV infection is widespread among subjects with cryptogenic chronic liver disease, as well as in liver diseases with features of autoimmunity (71.7% and 66.7% anti-HCV positive, respectively). Anti-HCV is infrequent among non drug-addicted HBsAg positive subjects (4.7%), and bears no relation to hepatitis D superinfection. Subjects with CLD and a history of parenteral exposure are almost always anti-HCV positive (89.2%). Patients with HBV-related CLD and previous drug-addicts are on the average younger than other disease groups, irrespective of their HCV status. Among subjects whose CLD is related to parenteral exposure, cryptogenic or autoimmune no increase in the rate of anti-HCV positivity seems to bear a parallel relationship to age. No known risk factor for parenteral transmission, other than use of blood or blood products and previous drug-addiction, can be clearly related to HCV infection. No trend to familiar clustering of HCV-induced liver disease is apparent. Liver disease severity, as assessed by transaminase levels and liver histology, does not correlate to anti-HCV status.

[Stability of complete dentures. 3]. / La stabilità nella protesi totale. Nota III.

The author analyzes the fundamental parameters of the complete denture; stability occlusal in the eccentric mandibular movements. They are: a) Correlation between condylar and incisal guide and occlusal morphology of the dental-arches. b) Presence of interincisive and intercanine functional free space.