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Examines the efficiency of immunoglobulin M antibody against hepatitis B core antigen in Italy. Discovery of hepatitis B virus by radioimmunoassay; Cause of hepatitis virus; Implications on the serum analysis.

Background: cemiplimab is an immunoglobulin G4 monoclonal antibody targeting the programmed cell death-1 receptor. A nominal use program is available in Italy in advanced cervical cancer (CC) patients treated with platinum based chemotherapy based on the results of EMPOWER-Cervical 1/GOG-3016/ENGOTcx9 trial. This real-world, retrospective cohort, multicenter study aimed at describing clinical outcomes of patients with advanced CC treated with cemiplimab in Italy., Methods: The primary objective of the study was to assess the feasibility and the replicability of the initial results in a real world setting of cemiplimab nominal use. The primary endpoint of our analysis was progression free survival (PFS). Secondary endpoints included overall response rate (ORR), overall survival (OS) and safety data., Results: From March 2022 to December 2023, 135 patients were treated in 12 Multicenter Italian Trials in Ovarian cancer and gynecologic malignancies (MITO) Centers. Forty-two percent of patients had one or more comorbidities, hypertension being the most common (23.4%). Median PFS was 4.0 months (range 3.0-6.0) and median OS was 12.0 months (12.0- NR) with no differences according to PD-L1 status. Complete response (CR) or no evidence of disease (NED) were observed in 8.6%; partial response (PR) in 21.1%, stable disease (SD) in 14.8% and progression was recorded in 44.5% of patients. Most common drug related adverse events (AEs) were anemia (39.1%) and fatigue (27.8%). Immune related AEs occurred in 18.0%., Conclusions: This study confirms the feasibility and the replicability of the cemiplimab nominal use in advanced CC, in a real-world practice in Italy., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Valentina Tuninetti: honoraria from MSD Oncology, GSK and EISAI, Elisa Virano: None declared, Vanda Salutari: Honoraria: AstraZeneca, MSD Oncology, GSK, PhamaMar, Novocure, Consulting: AstraZeneca, Novocure, Travel, Accomodations, Expenses: GSK, PharmaMar, Andrea Ricotti: None declared, Carmela Pisano: Advisory board: AstraZeneca, MSD Oncology, GSK, Monica Ducceschi: None declared, Giacinto Turitto: None declared, Giuseppa Scandurra: None declared, Maria Cristina Petrella: Honoraria from Astrazeneca, MSD, GSK, Valeria Forestieri: None declared, Monica Rizzetto: None declared, Serafina Mammoliti: None declared, Grazia Artioli: honoraria from AstraZeneca, MSD Oncology, GSK, Raffaella Cioffi: None declared, Lucia Borsotti: None declared, Marco Bellero: None declared, Chiara Rognone: None declared, Vittoria Carbone: None declared, Gabriella Ferrandina: None declared, Mara Mantiero: None declared, Carmen Azzolina: None declared, Eleonora Geninatti: None declared, Sandro Pignata: Research Funding: AstraZeneca, MSD Oncology, Roche, GSK, Pfizer, Honoraria: AstraZeneca, MSD Oncology, Roche, GSK, Novartis, EISAI, PharmaMar, Giorgio Valabrega: Consulting fees from GSK; honoraria from AstraZeneca, GSK, and MSD; travel support from AstraZeneca and PharmaMar; participation in advisory boards for AstraZeneca, EISAI, GSK, and MSD., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: The impact of narrow band imaging in improving the adenoma detection rate in a screening scenario is still unclear., Aim: To evaluate whether narrow band imaging compared with high definition white light colonoscopy can enhance the adenoma detection rate during screening colonoscopy., Methods: Consecutive patients presenting for screening colonoscopy were included into this study and were randomly assigned to the narrow band imaging group (Group 1) or standard colonoscopy group (Group 2). Primary end point was the adenoma detection rate and secondary aim was the detection rate of advanced adenomas., Results: Overall, 117 patients were allocated to Group 1 and 120 to Group 2. Both the adenoma detection rate and the detection rate of advanced adenomas were not significantly different between the two groups (respectively, 52.1% vs. 55%, RR=0.95, 95% CI 0.75-1.20; 32.5% vs. 44.2%, RR=0.74, 95% CI 0.53-1.02). No significant difference between the proportions of polypoid and flat adenomas was found. Male gender, no prior history of screening, and endoscopist's adenoma detection rate were independent predictive factors of higher advanced adenoma detection rate., Conclusions: In a screening scenario, narrow band imaging did not improve the adenoma nor advanced adenoma detection rates compared to high definition white light colonoscopy., (Copyright © 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background and Aims: Western guidelines consider radiofrequency ablation (RF) as the standard treatment for 'very early' and 'early' hepatocellular carcinoma (HCC) in nonsurgical cirrhotic patients. RF has also been proposed as the first-line therapy for 'surgical' candidates with a single nodule of 20 mm or less. The aim of this monocentric cohort study was to evaluate the technical and clinical outcomes of RF in the treatment of cirrhotic patients with a single HCC of 30 mm or less., Patients and Methods: We included all 209 consecutive patients treated between January 2001 and June 2011. The primary endpoints were the overall survival (OS) rate and safety; the secondary endpoints were primary technique effectiveness, local tumor progression, and the disease-free survival rate., Results: The 5-year OS rate of the entire sample was 44.3% (95% confidence interval: 36.7-55.8); Child-Pugh class B was the worst negative prognostic factor (hazard ratio: 2.06; P=0.008). A subgroup of 70 Child-Pugh class A patients suitable for surgical resection according to current Western operability criteria showed a 5-year OS rate of 60.6%. Treatment-related mortality and morbidity rates were 0 and 3.4%, respectively. Primary technique effectiveness rate was 95.2% after one to three RF sessions. The 5-year cumulative incidence of local tumor progression was 21.5 and 32.5% for nodules ≤20 and 21-30 mm, respectively. The 5-year disease-free survival rate (comprehensive of any kind of tumor progression or death) was 17.8% (95% confidence interval: 11.1-25.8)., Conclusion: RF is an effective and very safe therapy for HCC up to 30 mm; in 'surgical' cirrhotic patients, the OS rate was similar to those reported in surgical series, although the local recurrence rate was higher.

Background: Limited data are available on entecavir in Caucasian patients with HBV cirrhosis or chronic hepatitis B who are treated in the clinical practice. The aim was to evaluate the efficacy of entecavir in an Italian cohort of unselected patients with different stages of liver fibrosis, comparing the virological and clinical results obtained between patients with and without liver cirrhosis., Methods: Efficacy and safety of entecavir were retrospectively evaluated in 100 patients recruited in the Gastro-Hepatology Unit, San Giovanni Battista Hospital (Turin, Italy). A pharmacokinetic analysis was performed in 34 participants to assess whether cirrhosis may affect entecavir metabolism. Participants were followed-up for a median (range) duration of 21 months (2-108)., Results: Rates of virological response (negative viraemia by PCR for ≥ 2 consecutive determinations) after 12, 24 and 36 months were 91.7%, 97.5% and 93.7%, respectively. In the 84 patients who were treated for ≥ 12 months, presence of cirrhosis (OR 1.730, 95% CI 1.082, 2.766; P=0.022) and absence of hepatitis B e antigen (OR 0.479, 95% CI 0.273, 0.842; P=0.011) were independent predictors of earlier clearance of serum HBV DNA. There were no differences between the serum concentrations in the steady-state level of entecavir between patients with or without cirrhosis. No significant differences were detected between the average area under the curve in the means of the two groups (P=0.55)., Conclusions: Entecavir represents an excellent therapy in patients with HBV-related liver disease and particularly with cirrhosis where it showed a good profile of tolerability, higher efficacy and an earlier virological response.

Objectives: The response rate to treatment of chronic hepatitis C virus-genotype 1 and 4 infections was recently found to be strongly influenced by many polymorphisms. The aim of our study was to carry out an integrated analysis of the effects of polymorphisms and ribavirin (RBV) plasma exposure on outcome., Methods: The retrospective analysis included 174 patients. IL28B, CYP27B1, SLC29A1, SLC28A3, and SLC28A2 polymorphisms were genotyped and tested for association with sustained virological response. The impact of RBV plasma exposure during the first 3 months of therapy on outcome was also investigated., Results: Considering patients infected by hepatitis C virus-1/4, 3 polymorphisms (IL28B rs8099917TT, CYP27B1 rs4646536TT, and CNT2 rs11854484TT) were associated with sustained virological response. The number of negative variant allele and low RBV exposure were correlated to percentage increasing to therapy failure, suggesting some degree of cumulative effect of the 4 factors. A cutoff of 2.5 μg/mL of RBV was found to be associated with outcome (area under ROC [AUROC] curve = 0.64, sensitivity = 55.0%, and specificity = 71.2%, P = 0.020). In multivariate logistic regression analyses, each variant allele and RBV plasma exposure cutoff were independently associated with outcome., Conclusions: In this study, we found that additional polymorphisms and RBV plasma exposure are also able to influence the achievement of response. Regardless of the magnitude of RBV pharmacokinetic exposure, the negative predictive value of the polymorphisms here investigated is much stronger than the positive one.

Background: The long-term outcome in patients with chronic hepatitis C and type 2 diabetes mellitus treated with interferon and ribavirin is unclear. We compared incidence of liver-related events and mortality rates between hepatitis C virus-positive patients with or without diabetes mellitus, and the incidence of diabetes-related events between diabetic patients with and without hepatitis C., Methods: Retrospective study of 309 patients with chronic hepatitis C. Incidence of liver-related events, diabetes-related events and mortality rates were assessed over a mean follow-up of 11.02±4.9 years., Results: 50 (16%) chronic hepatitis C patients had diabetes mellitus. Diabetics showed a higher number of diabetes- and liver-related events than non-diabetics (10% vs 1.5%, p=0.006; 18% vs 5.7%, p=0.007, respectively) with a mortality of 14% vs 1.5% (p=0.0003). Baseline cirrhosis (p=0.002) and non-sustained virological response (p=0.01) were independent risk factors for liver events; diabetes mellitus (p=0.01) and hypertension (p=0.0017) were independent factors for diabetes-related events., Conclusions: In patients with chronic hepatitis C, comorbidity with diabetes mellitus was associated with a higher mortality rate and incidence of liver/diabetes-related events. Independent risk factors for liver-related events were the non-response to antiviral therapy and cirrhosis at baseline., (Copyright © 2011 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

The Italian recommendations for the therapy of hepatitis B virus (HBV)-related disease were issued in 2008. Subsequently in 2008 the nucleotide analogue (NA) Tenofovir was approved for antiviral treatment. The introduction of this important new drug has called for the current guidelines update, which includes some additional revisions: (a) the indication for therapy is extended to mild liver fibrosis and the indication for treatment is graded as "possible", "optional" or "mandatory" according to the fibrosis stage; (b) two different treatment strategies are described: first line definite duration treatment with interferon, long-term treatment of indefinite duration with NA; (c) the indication to follow either strategy is also based on the stage of liver fibrosis; (d) virological monitoring is modified to include the definitions of failure and of sustained virological response to interferon therapy; (e) the recommendation to use HBV DNA assays with high sensitivity and wide linear ranges is underlined (f) guidelines on post-treatment follow-up after finite treatment with NA, potential side effects of therapy and non-virological monitoring are defined; (g) definitions and treatment of patients without optimal response to NA are reported; (f) treatment and monitoring of compensated or decompensated cirrhosis and hepatocellular carcinoma are updated., (Copyright © 2010 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background & Aims: To investigate the impact of HDV infection on morbidity and mortality of patients., Patients and Methods: This was a retrospective study on 188 patients that underwent a program of periodic surveillance until 2008. The demographic data, stage of liver disease, treatment efficacy, development of liver complications (ascites, oesophageal bleeding, encephalopathy), and survival were registered. A Cox regression analysis was carried out to determine the impact of viral and patient features on survival., Results: At baseline, 126 patients (67%) tested positive for serum IgM anti-HDV antibodies, 171 (91%) for anti-HBe, 175 (93%) for serum HDV-RNA, and 61 (33%) for serum HBV-DNA. Eighty-two patients (43%) had chronic hepatitis at histology; the remaining 106 individuals had a clinical/histological diagnosis of cirrhosis. Ninety-six patients received interferon (n = 90) or lamivudine (n = 6) therapy, and 27 of them (30%) attained a sustained response. During follow up, 21 patients with chronic hepatitis progressed to cirrhosis. Of the 127 cirrhotic patients, hepatic decompensation occurred in 42 patients (33%) and hepatocellular carcinoma in 17 (13%). The 5- and 10-year survival free of events were 96.8% and 81.9%, respectively, for patients with chronic hepatitis, and 83.9% and 59.4% for cirrhotics (p<0.01). At multivariate analysis, lack of antiviral therapy (p = 0.01), cirrhosis at presentation (p<0.01), and male sex (p = 0.03) independently predicted a worse outcome., Conclusion: HDV liver disease lasts several decades. Half of all patients who develop cirrhosis later will advance to liver failure. At present, interferon therapy is recommended as soon as possible to slow or alter the natural course of liver disease., (Copyright © 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Aim: Since the major established risk factors explain the pathogenesis of ischemic heart disease (IHD) in a proportion of cases, it is crucial to search for other causal mechanisms. The possible link between IHD and Helicobacter pylori (H.pylori) infection has been reported. However, the precise mechanism of this potential relationship, by a proinflammatory activity or metabolic disorder, is unclear. In order to investigate this issue, the authors assessed changes in clinical and biochemical parameters related to IHD after bacterial eradication., Methods: A total of 496 patients (281 males; mean age 59.7+/-2.3) with H.pylori-positive dyspepsia and/or peptic ulcer were studied after cure of the bacterium. H.pylori status was determined by histology or 13C-urea breath testing. Examinations for body mass index, diastolic blood pressure and blood testing (C-reactive protein, fibrinogen, triglycerides, total cholesterol, high-density and low-density lipoprotein cholesterol, fasting glucose) were performed before eradication and annually for up to five years thereafter. For statistical analyses, the Student's t test was performed., Results: HDL-C increased (P=0.02) while C-reactive protein and fibrinogen levels diminished (P<0.0001) significantly. BMI and diastolic blood pressure increased in a significant (P=0.032 and P=0.039 respectively) manner compared to baseline., Conclusions: H.pylori eradication is associated with modification of some clinical and biochemical parameters related to IHD during a follow-up of five years. There is a need for large interventional randomized studies in order to prove a causal association.

Background: Preliminary evidence of cases of acute occult hepatitis B virus (HBV) infection (OBI) has been recently reported in the literature. Furthermore, OBI definition has been the object of an international consensus conference., Study Design and Methods: A case of acute primary OBI was identified and followed up in a repeat female blood donor using a highly sensitive nucleic acid test (NAT; Procleix Ultrio on Tigris, Chiron). Genotyping and sequencing of virus isolates from donor and contact cases were performed., Results: The blood donor never developed detectable hepatitis B surface antigen (HBsAg) until seroconversion to antibody to hepatitis B surface antigen/antibody to hepatitis B core antigen. A very low viral load was observed during the infection course (<50 IU/mL). Donor HBV DNA sequencing consistently showed a CCA deletion leading to amino acid T116 deletion in the small envelope protein (S). Other sequence features showed high homology between donor and contact case, suggesting a sexual transmission., Discussion: The main explanation for HBsAg undetectability relies on the very low level of viremia observed. The single-amino-acid deletion found in the S protein cannot account for HBsAg detection failure, because the capture antibody of the assay used is targeted to a different sequence epitope (aa121-124). Meanwhile, CCA deletion may have impacted the virus replication efficiency since it affects the overlapping reverse transcriptase "finger" domain of the polymerase gene. These findings define this case as an acute primary OBI, confirming the existence of this condition. NAT with high sensitivity is the only screening enabling prevention of HBV transmission by transfusion in such cases.

Aim: Triple therapy consisting of a proton pump inhibitor (PPI) and two antibiotics is used as first choice in treating Helicobacter pylori (H. pylori) infection. Since in the North Italian population, metronidazole resistance is less than 40%, this antibiotic would be preferable as first approach. The aim of this randomized study was to assess the efficacy of a metronidazole-based versus a tinidazole-based treatment, in naïve patients with H. pylori infection., Methods: Diagnosis and eradication of H. pylori infection were assessed by 13C-urea breath test, and by histology when an endoscopic examination was necessary. A total of 171 patients was treated: 91 (47 males, mean age 50+/-3 years) with metronidazole 250 mg q.i.d., amoxicilline 1 gr b.i.d. and PPI standard dose (MAO), and 80 (36 males, mean age 52+/-3.8 years) with tinidazole 500 mg b.i.d., amoxicilline 1 gr b.i.d. and PPI standard dose (TAO) regimen for 7, 10 or 14 days., Results: Three patients suspended MAO treatment due to side effects. H. pylori eradication was obtained as follow indicated. After 7 days, in 23/30 (76.6%) patients in MAO versus 20/27 (74.0%) in TAO regimen. After 10 days, in 20/26 (76.9%) patients in MAO versus 20/26 (76.9%) in TAO regimen. After 14 days, in 25/32 subjects (78.1%) in MAO versus 21/27 (77.7%) in TAO treatment. The differences among durations or between metronidazole-versus tinidazole-based triple therapy were not statistically different., Conclusion: Treatment with metronidazole is as effective as that with tinidazole in terms of efficacy. Moreover, duration did not influence efficacy of treatment.

The changing scenario of hepatitis B virus therapy has encouraged the organisation of a workshop, endorsed by three Italian scientific societies, aimed at defining the current recommendations for hepatitis B virus treatment. Liver histology and stage of disease remain fundamental for treatment decisions; interferon and nucleoside/nucleotide analogues-based therapy represent different strategies for different phases of the hepatitis B virus disease. The recommendations defined: new and lower cut-off of hepatitis B virus-DNA for eligibility to therapy according to disease stage, how to optimise the use of nucleoside/nucleotide analogues and to individualise the monitoring of response and what to do with treatment failures. Specific recommendations have also been given for cirrhosis patients, those immune suppressed and co-infected with HIV and other hepatitis viruses.

Background and Objectives: Occult hepatitis B virus (HBV) infection might allow the release of viremic units into the blood supply network if blood is tested only for hepatitis B surface antigen (HBsAg). The aim of our study was to evaluate the actual prevalence, viral load and genotype of occult HBV infections among first-time blood donors in north-western Italy and to suggest a way to minimize risks of transmission of this infection., Design and Methods: We assayed 6313 consecutive blood donors for antibodies to HBV core antigen (anti-HBc) in addition to mandatory screening. HBsAg-negative/anti-HBc-positive donors were assayed for antibodies to HBsAg (anti-HBs) and for HBV-DNA using COBAS Ampliscreen HBV (Roche) on individual donations. All HBV-DNA-positive samples underwent confirmatory testing with additional polymerase chain reaction-based assays., Results: The prevalence of anti-HBc positive subjects was 4.85%. Fourteen out of 288 blood donors (4.86%) were confirmed to have circulating HBV-DNA at a low level (range 8-108 IU/mL). All viremic donors were also anti-HBs-positive., Interpretation and Conclusions: We estimate that in north-western Italy up to 2298 units per million donated units from first-time donors may contain HBV-DNA. The risk of an HBV-DNA positive unit from an occult carrier being released into the blood supply is more than 100 times higher than the estimated residual risk related to the window phase of HBV infection in our country. The potential infectivity of these units is debated, but their use cannot be considered safe at least in immunocompromised patients.

The evolving role of liver biopsy has induced the formulation of several guidelines on its appropriateness. However, the great divergence among hepatologists is still unresolved. We report the 4-year activity of a day hospital of gastrohepatology in northern Italy. Between January 2001 and July 2004, 835 subjects (mean age, 43+/-12 years) underwent this procedure in our facility. Etiologically, in 465 (56%) and 157 (19%) patients, chronic hepatitis C and nonspecific elevated liver biochemical tests were the first and second indications, followed by chronic hepatitis B and suspected nonalcoholic steatohepatitis. On a purpose basis, procedures requested for staging (n = 578) and/or for diagnosis (n = 217) were identified. Among the former, 80% had the scope of staging chronic hepatitis C, and in 15% of these unsuspected superimposed cirrhosis was detected. Among diagnostic procedures, nonspecific raised liver enzyme level ranked first. Twenty-two percent of patients reported unwanted effects following the procedure. In conclusion, these data accord with indications expressed by international guidelines. The impact of liver biopsy on therapeutic decision-making needs to be studied further.

Background: Capsule enteroscopy is considered the gold standard for evaluating patients with obscure gastrointestinal bleeding. The costs of capsule enteroscopy examination, however, make it uncertain whether the clinically relevant diagnostic gain is also associated with cost savings., Aim: To evaluate the incremental cost-effectiveness ratio of capsule enteroscopy in patients with obscure gastrointestinal bleeding., Methods: Retrospective study was carried out in nine Italian gastroenterology units from 2003 to 2005. Data on 369 consecutive patients with obscure gastrointestinal bleeding were collected. The diagnostic yield of capsule enteroscopy vs. other imaging procedures was evaluated as a measure of efficacy. The values of Diagnosis Related Group 175 (euro 1884.00 for obscure-occult bleeding and euro 2141.00 for obscure-overt bleeding) were calculated as measures of economic outcomes in the cost analysis., Results: Obscure and occult gastrointestinal bleeding was recorded in 177 patients (48%) with a mean duration of anemia history of 17.6+/-20.7 months. Among patients, 60.9% had had at least one hospital admission, 21.2% at least two, and 1.2% of obscure bleeders up to nine admissions. Overall, 58.4% of patients had positive findings with capsule enteroscopy compared with 28.0% with other imaging procedures (P<0.001). The mean cost of a positive diagnosis with capsule enteroscopy was euro 2090.76 and that of other procedures was euro 3828.83 with a mean cost saving of euro 1738.07 (P<0.001) for one positive diagnosis., Conclusions: Capsule enteroscopy is a cost-saving approach in the evaluation of patients with obscure gastrointestinal bleeding.

Aim: Given the demographic shifts and needs of cost rationalization, it is of high priority to organize health care on the basis of ambulatory outpatients models. The aim of this study was to examine activity at the gastro-hepatology outpatients clinic of the Molinette Hospital. In this facility, the management is based on a work team organization that follows cohorts of patients with specific pathologies., Methods: All services, consultations and urea breath test (UBT) for the diagnosis of Helicobacter pylori infection, carried out from January 2003 to December 2006, were extrapolated from the computerized system. Consultations were divided into first examination and controls. Furthermore, the destination of the patients after each consultation was considered., Results: During the year 2003, 8 842 consultations and 4 071 UBT were carried out, in the year 2004, 11 342 consultations and 2 409 UBT, in the year 2005, 12 474 consultations and 2 510 UBT, in the year 2006, 12 249 consultations and 2 357 UBT. No further specialistic management was required for 25% of patients, while 2% had been hospitalized in the bed unit, 3% in the short hospitalization unit or the day-hospital. The remaining 70% were included in work teams or monitored thereafter. The comparison with consultations from 1994 shows an increase due to both first examination (+300%) and controls (+83%)., Conclusions: The burden of the requests from the population and primary care structures addressed to the outpatients clinic of gastro-hepatology is relevant. The activity of this facility leads to a low rate of hospitalization as well as of cost reduction.

Aim: To investigate the seroprevalence of Helicobacter pylori (H pylori) infection and its more virulent strains as well as the correlation with the histologic features among patients who had undergone surgery for gastric cancer (GC)., Methods: Samples from 317 (184 males, 133 females, mean age 69+/-3.4 years) consecutive patients who had undergone surgery for gastric non-cardia adenocarcinoma were included in the study. Five hundred and fifty-five (294 males, 261 females, mean age 57.3+/-4.1 years) patients consecutively admitted to the Emergency Care Unit served as control. Histological examination of tumor, lymph nodes and other tissues obtained at the time of surgery represented the diagnostic "gold standard". An enzyme immunosorbent assay was used to detect serum anti-H pylori (IgG) antibodies and Western blotting technique was utilized to search for anti-CagA protein (IgG)., Results: Two hundred and sixty-one of three hundred and seventeen (82.3%) GC patients and 314/555 (56.5%) controls were seropositive for anti-H pylori (P<0.0001; OR, 3.58; 95%CI, 2.53-5.07). Out of the 317 cases, 267 (84.2%) were seropositive for anti-CagA antibody vs 100 out of 555 (18%) controls (P<0.0001; OR, 24.30; 95%CI, 16.5-35.9). There was no difference between the frequency of H pylori in intestinal type carcinoma (76.2%) and diffuse type cancer (78.8%). Intestinal metaplasia (IM) was more frequent but not significant in the intestinal type cancer (83.4% vs 75.2% in diffuse type and 72.5% in mixed type). Among the patients examined for IM, 39.8% had IM type I, 8.3% type II and 51.9% type III(type III vs others, P = 0.4)., Conclusion: This study confirms a high seroprevalence of H pylori infection in patients suffering from gastric adenocarcinoma and provides further evidence that searching for CagA status over H pylori infection might confer additional benefit in identifying populations at greater risk for this tumor.

The first Italian liver transplant center to reach the goal of 1000 procedures was Turin. The paper reports this single-center experience, highlighting the main changes that have occurred over time. From 1990 to 2002, 1000 consecutive liver transplants were performed in 910 patients, mainly cirrhotics. Surgical technique was based on the preservation of the retrohepatic vena cava of the recipient. The veno-venous bypass was used in 30 cases only and abandoned since 1997. Operating time, warm ischemia time and length of hospital stay significantly decreased over the years, while operating room extubation became routine. Immunosuppression pivoted on cyclosporine A. Management of retransplantations, marginal grafts, and of HCV-positive, HBV-positive and hepatocellular carcinoma recipients were optimized. Median follow-up of the patients was 41 months. Overall survival rates at 1, 5 and 10 years were 87%, 78% and 72% respectively. Survival rates obtained in the second half of the cases (1999-2002 period) were significantly better than those obtained in the first half (1990-1998 period) (90% vs. 83% at 1 year and 81% vs. 76% at 5 years respectively). Increasing experience in liver transplant surgery and postoperative care allowed standardization of the procedure and expansion of the activity, with parallel improvement of the results.

Background: The potential role of digestive endoscopy as a mode for transmission of hepatitis C virus (HCV) is controversial., Objective: To evaluate the role of digestive endoscopy in transmitting HCV by comparing the incidence of HCV infection in a cohort of patients undergoing endoscopy and in a cohort of blood donors., Design: Prospective cohort study., Setting: 3 endoscopic units and 2 blood banks in northwestern Italy., Patients: The potentially exposed cohort consisted of 9188 outpatients consecutively recruited from 3 endoscopic units. Of 9008 patients negative for antibody to HCV (anti-HCV), 8260 (92%) were retested for anti-HCV 6 months after endoscopy. The unexposed cohort consisted of 51,230 healthy, anti-HCV-negative persons who donated blood at 2 blood banks in the same area and during the same time period; 38,280 of them (75%) were tested again for anti-HCV 6 to 48 months after the first blood donation (95,317 person-years of observation)., Measurements: Differences in the anti-HCV seroconversion rate between the exposed cohort (patients undergoing endoscopy) and the unexposed cohort (blood donors). Seroconversion was evaluated by a third-generation enzyme immunoassay for anti-HCV; persons positive for anti-HCV were tested for HCV RNA by polymerase chain reaction., Results: All 8260 persons undergoing endoscopy remained negative for anti-HCV 6 months after the procedure (risk per 1000 persons, 0 [95% CI, 0 to 0.465]); in particular, none of the 912 patients who underwent endoscopy with the same instrument previously used on HCV carriers showed anti-HCV seroconversion (risk per 1000 persons, 0 [CI, 0 to 4.195]). Four blood donors became positive for anti-HCV and HCV RNA (mean follow-up, 2.49 years; 0.042 case per 1000 person-years [CI, 0.011 to 0.107 case per 1000 person-years]); each had undergone minor surgery before the second test., Limitations: In the endoscopy cohort, 8.3% of patients were lost to follow-up., Conclusions: These findings support the hypothesis that properly performed digestive endoscopy is not a major risk factor for the transmission of HCV.

Background/aims: This study assess prevalence, risk factors, and clinical and virological features of dual hepatitis B virus (HBV)/hepatitis C virus (HCV) infection., Methods: We evaluated 837 hepatitis B surface antigen positive patients, prospectively enrolled in 14 Italian units., Results: Anti-HCV was present in 59 cases (7%); age specific prevalences were 4.5% (0-30 years), 4.4% (>30-50) and 14% (>50). Independent predictors of dual infection were age >42 years, history of I.V. drug use (IDU), blood transfusion and residence in the South of the country. The strength of the association with IDU was high, but this exposure accounted for five coinfection cases only. Cirrhosis was present in 107 of the 709 patients with HBV alone (15.1%), in 30 of 69 with hepatitis D virus coinfection (43%) and in 17 of 59 with HCV coinfection (28.8%); a light alcohol use was marginally associated with cirrhosis. Of 36 B/C coinfected patients, 16 (44.4%) had only HBV-DNA in serum, (median age=47.5 years) five (13.9%) had both HBV-DNA and HCV-RNA (age=53), nine (25%) had HCV-RNA alone (age=59) and six (16.7%) tested negative for both., Conclusions: This study depicts the epidemiological and clinical burden of dual HBV/HCV infection in Italy.

Background: Infection by Helicobacter hepaticus causes chronic hepatitis and hepatocellular carcinoma (HCC) in mice, and Helicobacter pylori (H. pylori) genomic sequences have been demonstrated in the liver of patients with HCC. H. pylori infection reportedly occurs with high frequency in patients with cirrhosis but none of the studies has investigated it in subjects with cirrhosis and superimposed HCC. In this case-control study, we searched for the seroprevalence of H. pylori infection in patients with HCC., Patients and Method: Forty-six patients (30 males, 16 females, mean age 69 years) with HCC and hepatitis C virus (HCV)-related cirrhosis were compared to 46 sex and age (+/-1 year) matched patients presenting consecutively to the Emergency Department of Molinette Hospital of Torino. All subjects were tested for presence in serum of IgG antibodies against H. pylori and the result was analyzed using the chi-square test., Results: H. pylori seropositivity was more prevalent among patients with HCC (36/46, 78.2%) than in controls (25/46, 54%) (P<0.05) (OR 3.02, 95% confidence interval ). Twenty-five out of 30 (83.3%) male patients showed seropositivity at a variance with 16/30 (53%) in the controls (P<0.05); 11 out of 16 (68.7%) female patients were seropositive versus 9 out of 16 (56.2%) control subjects (P=n.s.)., Conclusion: Seroprevalence of antibodies to H. pylori was found to be higher in patients with HCC than in controls.

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.

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.

Background: Hepatitis C virus infection (HCV) is a major cause of chronic liver disease with the risk of evolution towards hepatic cirrhosis and hepatocellular carcinoma. Numerous studies have documented the possibility of HCV transmission through blood transfusions during surgery or during intravenous drug use. The percentage of the risk of sexual transmission, in the general population not presenting the aforesaid risks is still very controversial. The aim of this study was to evaluate the concomitant levels of seropositivity for anti-HCV, in the partners of patients with chronic HCV liver disease, but no history of previous transfusions or use of intravenous drugs., Methods: The study included 196 anti-HCV positive spouses with a clinical diagnosis of active chronic hepatitis, aged between 20 and 75 years (mean age 53 years, SD+/-11 years). HCV infection was diagnosed by positivity of serum samples for anti HCV (EIA), confirmed by RIBA II and by circulating HCV-RNA detected by polymerase chain reaction (PCR). All partners underwent anti-HCV assay (EIA), confirmed by RIBA II in the event of positivity., Results: The mean period of cohabitation was 27 years (range 3-37, SD+/-9.8 years). The positivity of anti HCV in both subjects affected 11 couples (5.6%). Of these couples, the viral genotype was also available in 3 cases which proved to be identical in the index patient and the partner, whereas it was not possible to identify the genotype in other couples owing to scarce compliance., Conclusions: The data obtained from this study confirm the possibility of the sexual transmission of HCV. However, in the context of subjects not belonging to "high risk" groups, this method of transmission does not appear to be important if compared with that of other viruses (HBV and HIV).

This study was aimed to evaluate TT virus prevalence in subjects with hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infections in patients affected by hepatitis of unknown origin (non-A-non-E hepatitis) and in healthy subjects who had not been exposed to HBV, HCV and HIV. A total of 317 subjects were tested; 40 were HBsAg asymptomatic carriers, 57 subjects were anti-HCV positive (45 without chronic hepatitis and 12 with HCV-related chronic hepatitis), and 27 had chronic non-A-non-E hepatitis. Fifty-seven subjects were intravenous drug users (IVDUs) (52 with HCV or/and HIV infections), seven patients underwent a liver transplant for fulminant hepatitis and 137 were healthy subjects from the general population. Overall, TTV-DNA was detected in 62 subjects (19.6%): in 17.9% of the HBsAg carriers, in 14% of the anti-HCV-positive patients (in 8.3% and in 15.5% of patients with and without chronic hepatitis, respectively), in 22.2% of non-A-non-E hepatitis patients, in 22.8% of IVDUs, in 57.1% of fulminant hepatitis patients. TTV-DNA was also found in 20.4% healthy subjects. The prevalence in the different subgroups was not statistically different. The genotypes were identified in 40 of the 62 (64.5%) TTV-DNA positive samples: genotype 1a in 17.5%, 1b in 27.5%, genotype 2 in 27.5%, genotype 3 in 15.0%, genotype 4 in 5.0% and genotype 5 in 7.5%; the genotype distribution in the subsets of patients was not significantly different. In conclusion, this study showed that TTV infection is common in Italy; it is widespread throughout the entire population and five genotypes are present in Sardinia. Our results further dismiss the role of TTV as cofactor in influencing the clinical course of infections with other hepatitis viruses as well as the role of HIV in enhancing TTV transmission and replication.

Background: Digestive diseases (GI) have a major impact on public health in Italy. Hospital stay for digestive pathologies parallels that due to cardiovascular causes. Total mortality for GI causes is also very high. The management of GI pathologies is therefore a major task for the National Health System. To the experienced gastroenterologist it is clear that a large number of hospitalisation is linked to a lack of careful outpatient follow-up of diseases such as cirrhosis, ulcerative colitis and peptic ulcer., Methods: One year of activity of our Gastro-entero-Hepatology outpatient service is examined. The management of the majority of GI diseases is organized in working teams of physicians and surgeons following cohorts of patients suffering of a specific disease., Results: During the year 2000 not only a statistically significant higher number of patients has been examined (p<0.05), in comparison with 1994, but also the hospitalisation rate was lowered resulting in a very significative cost-containment., Conclusions: The specialization of outpatient activities into working teams offers advantages in terms of more appropriate medical care and cost reduction, partly due to a less frequent hospitalisation. The obvious counterpart was an increase of request of such form of follow-up from patients, resulting in longer delay to the access.

Hepatitis delta virus (HDV) was responsible for a high proportion of cases of acute and chronic liver disease in Southern Europe during the 1970s. Some data suggest that by the 1990s HDV circulation had substantially declined. We have assessed the prevalence of HDV infection and its clinical impact in 834 Italian hepatitis B surface antigen (HBsAg) carriers in 1997. Anti-HDV antibodies were sought in all consecutive chronic HBsAg carriers observed in 14 referral liver units throughout Italy. Risk factors for anti-HDV positivity were evaluated. Anti-HDV antibodies were found in 69 of 834 (8.3%) HBsAg-positive patients. Cohabitation with an anti-HDV-positive subject, intravenous drug addiction, residence in the South of the country, and the presence of cirrhosis were independently associated with the presence of anti-HDV antibodies. The overall prevalence of anti-HDV antibodies was lower than those observed in 2 multicenter surveys performed in 1987 and 1992 (23% and 14%, respectively). By 1997, the percentage of anti-HDV-positive subjects had sharply decreased in the 30 to 50 years age group, whereas it was almost unchanged in subjects over 50 years of age. The highest prevalence of anti-HDV antibodies (11.7%) was found in patients with cirrhosis. This prevalence was as high as 40% in the 1987 study. The circulation of HDV sharply decreased in Italy, by 1.5% per year, from 1987 to 1997. This decrease resulted mainly from the reduction in chronic HDV infections in the young, for whom high morbidity and mortality rates were recorded in the past. The results anticipate the almost complete control of HDV infection in the near future.

Liver cirrhosis is a significant cause of death in Italy and one of the most frequent causes of hospitalization. The burden of cirrhotic patients on the National Health System is extremely high due to the frequent need for medical care. Acute peptic ulcer and upper gastrointestinal bleeding reportedly occur in over one-third of cirrhotic patients. Since Helicobacter pylori (H. pylori) infection strongly correlates with peptic ulcer, we wished to ascertain the prevalence of H. pylori infection in cirrhotic patients. In a case-control study we looked for this infection in 45 consecutive male patients suffering from hepatitis B virus (HBV)-related cirrhosis and 310 sex and age matched blood donors resident in the same area. Antibodies against H. pylori were present in 40/45 (89%) patients and 183/310 (59%) blood donors (P<0.001). This very high prevalence of H. pylori may explain the frequent occurrence of gastroduodenal ulcer in cirrhotic patients. (See Editorial p. 203)

Field studies in large numbers of subjects unselected for risk factors are needed to assess the true prevalence and health burden of hepatitis C virus (HCV) infection. We assessed the prevalence, virological characteristics, risk factors and evidence of liver disease in a population of healthy subjects from an urban area of Sardinia. Hepatitis B virus (HBV) markers were also studied. The prevalence of antibodies to HCV (anti-HCV) (recombinant immunoblot assay [RIBA]-confirmed positive results) was 3.19% in 3324 workers and 7.11% in 225 elderly subjects, with a cumulative anti-HCV prevalence of 2.70% (95% CI 2.17-3.24). Males were more frequently positive than females (P < 0.01). The age-specific prevalence of HCV infection increased progressively in females. It showed two peaks in males: one in the fourth decade, the other in the seventh decade. HCV RNA was detected in 63.16% of the RIBA-positive sera, in 10% of the RIBA indeterminates and in none of the RIBA-negative specimens. Only 1.75% of anti-HCV-positive subjects had elevated transaminases. The frequency of HCV genotype 1b was 32.79%; of 1a, 21.31%; of 3a, 19.67%; of 4, 13.11%; and of 2a, 13.11%. HBV markers were found in 28.03% of workers. On multivariate analysis, male gender and tattooing were significantly associated with HCV and HBV infections: transfusion and travel with HCV, and age over 40 with HBV. The age prevalence rates of HCV infection in the Cagliari area reflect different risk factors that have been operative at different times. In this urban area, the large majority of HCV infections run a subclinical course.

To identify correlations between the distribution of hepatitis C virus (HCV) genotypes and demographic, pathological and virological parameters of HCV-infected patients, we prospectively recruited 650 patients with biopsy-proven chronic hepatitis C without histological aspects of cirrhosis; none had been treated with antiviral therapy. Data regarding gender, age, mode of HCV transmission, alanine aminotransferase (ALT) and HCV RNA levels, immunoglobulin M (IgM) anticore values, liver histology and histological activity were obtained from each patient and correlated on multivariate analysis with infecting HCV genotype. Fifty-five per cent of the patients were infected with HCV genotype 1, 20% with HCV genotype 2, 18% with HCV genotype 3 and 7% with HCV genotype 4. Non-transfusional HCV transmission, low ALT levels, IgM anticore reactivity and a low histological grading score were independent variables associated with HCV genotype 1. Older age, female gender, post-transfusional transmission and a high histological grading score were related to HCV genotype 2, whilst younger age, history of current/previous drug abuse, high ALT values, low IgM anticore reactivity and high viraemic levels were associated with HCV genotype 3. History of illicit use of intravenous drugs and low HCV RNA levels were the only independent variables correlated with HCV genotype 4. Genotype 1 remains predominant in Italy but the prevalence of HCV genotypes is changing in relation to age and mode of transmission: Italian patients with HCV genotype 3 are younger and exhibit higher levels of ALT and HCV RNA than patients with other genotypes.

Background: The classical risk factors for acute myocardial infarction (AMI) fail to explain all the epidemiological variations of the disease. Among the new risk factors recently reported, several infectious agents appear to increase the risk of AMI. In particular, acute and chronic respiratory diseases due to Chlamydia pneumoniae, and Helicobacter pylori (H. pylori) infection seem to be strongly involved. The aim of this work is to determine the prevalence of H. pylori infection in a group of male patients with AMI, in a case-control study, where a group of blood donors matched for sex and age served as control. We searched for the classical risk factors in all patients., Methods: We studied 212 consecutive male patients, aged 40-65 years, admitted for AMI at the Coronary Care Units at Hospitals in three towns of Northern Italy. H. pylori infection was assessed by the highly specific and sensitive 13C-urea breath test and by presence of antibodies (IgG) against H. pylori in circulation. Volunteer blood donors attending our Hospital Blood Bank served as controls. Among the patients we investigated the presence of hypertension, cholesterol and glucose levels in serum, fibrinogen in plasma and the smoking habit., Results: H. pylori infection was present in 187/212 (88%) of the patients and in 183/310 (59%) of the control population (p < 0.0001). Classical risk factors for AMI did not differ among patients with and without H. pylori infection., Conclusion: Patients admitted to the Coronary Care Unit for acute myocardial infarction had a notably higher prevalence of H. pylori infection than the general population. The classical risk factors for coronary disease were equally present in all patients with AMI irrespective of H. pylori status.

Background & Aims: The aim of this study was to assess changes in the clinical pattern of hepatitis D virus (HDV) infection in Italy, brought about by improved control of hepatitis B and D viruses, and to establish the natural history of chronic hepatitis D., Methods: Histological diagnosis and clinical features of 122 patients with HDV recruited from 1987 to 1996 in three Italian tertiary referral centers (Torino, northern Italy; San Giovanni Rotondo and Castellana Grotte, southern Italy) were compared with those of 162 patients collected in the same centers in the previous decade. Patients from both groups with at least 6 months of follow-up were included in a new subgroup to assess the natural history of the disease., Results: Among 162 patients referred from 1977 to 1986, 9 (6%) had mild hepatitis at histology vs. 9 (8%) of 122 patients referred in the second decade; 105 (65%) vs. 21 (17%) had severe hepatitis; 46 (28%) vs. 38 (31%) had histological asymptomatic cirrhosis; and 2 (1%) vs. 54 (44%) had clinically overt cirrhosis. For 159 patients (121 men and 38 women; mean age, 34 +/- 11), a follow-up of more than 6 months was documented, and they were included in the natural history subgroup. After 78 +/- 59 months of follow-up, 112 (70%) survived free of liver transplantation: 9 underwent transplantation, 32 died of liver failure, and 6 of acquired immunodeficiency syndrome. Estimated 5- and 10-year probability of survival free of orthotopic liver transplantation was 100% and 100% for patients with mild hepatitis, 90% and 90% for severe hepatitis, 81% and 58% for histological asymptomatic cirrhosis, and 49% and 40% for clinical cirrhosis (P < 0.01), respectively., Conclusions: Occurrence of fresh and severe forms of hepatitis D has diminished greatly in Italy. Contemporary patients represent cohorts infected years ago who survived the immediate medical impact of hepatitis D. The disease has been asymptomatic and nonprogressive in a minority; in the majority, it rapidly advanced to cirrhosis but thereafter subsided with stable clinical conditions for more than a decade.

Background/aims: Epidemiologic studies have suggested that transmission of hepatitis delta virus (HDV) occurs by intrafamilial routes in some populations in southern Italy, where HDV infection is endemic. To further evaluate intrafamilial transmission of HDV, we obtained the partial sequence of the viral genome from HDV-RNA positive members of families in which two or more immediate family members were positive for HDV-RNA., Methods: The region analyzed was the semi-conserved region from nucleotides 908 to 1265. Sequences obtained from family members were compared with those obtained from a control group of 20 unrelated patients., Results: The mean genetic divergence among HDV isolates was 2.8 +/- 1.7% within the 9 families analyzed, and 7.6 +/- 2.2% among the control group of unrelated individuals (p < 0.0001). A Receiver Operating Characteristic curve and Youden Index were used to define a cut-off value of 3.5% to discriminate sequence variations calculated within families and in the control group., Conclusions: The data indicate that in most family units, HDV-infected members harbored nearly identical strains of HDV, and provide molecular support that HDV infection can be transmitted within the family. Such spreading among family members highlights the role of inapparent transmission through personal contacts.

The sera of 46 Italian patients with chronic hepatitis delta virus (HDV) infection were analyzed for HDV RNA by polymerase chain reaction (PCR) amplification. Genetic analysis of sequences amplified from two regions of the HDV genome indicated that all HDV RNA-positive patients (98%) were infected with HDV genotype I. In Italy, infection with this genotype appeared to be associated with a broad spectrum of chronic disease. No subtypes of HDV genotype I were identified, nor were genetic variations clearly associated with different disease patterns; however, clustering of some sequences suggested correlations with geography and transmission route. Italian HDV genotype I sequences were more diverse than those from east Asia and North America, suggesting that HDV genotype I was likely introduced to Italy earlier and/or from multiple sources as compared to those areas. All sequences analyzed were predicted to fold into the unbranched rod structure typical of HDV RNA. Within this structure, three conserved features were identified, including sequences around the RNA editing site and the polyadenylation signal site. We conclude that in Italy, where HDV infection has been endemic, the overwhelmingly predominant genotype of HDV is genotype I.

The Prospective Payment System uses Diagnosis-Related Groups (DRG) as a reimbursement system. DRG 202 is a disease-related group including liver cirrhosis as a whole. Patients referring to the inpatient unit complain of variable severity and complications of cirrhosis, possibly implying different expenditure of resources. Aim of the investigation was to identify factors affecting cost variability in patients with cirrhosis. A total of 73 consecutive, DRG 202-assigned, cirrhotic patients classified according to demographic and clinical variables were evaluated for length and costs of hospitalization calculated on a full-cost basis. Mean length of hospitalization was 10.2 +/- 7 days. Mean cost of hospitalization was Lit. 4.348.000 +/- 2.718.000. Medical, nursing, diagnostic, drug and general charges accounted for 13%, 29%, 37%, 5% and 16% of the cost, respectively. Child-Pugh score significantly correlated with drug consumption (p < 0.005), length (p < 0.01) and costs (p < 0.001) of hospitalization, but not with cost per day. Age, sex, admission status, referral reason, associated diseases and liver transplant susceptibility did not correlate with duration and costs of hospitalization. Disease severity significantly modifies costs of hospital admission in cirrhotic patients mostly on account of longer hospital stay. Surrogate indexes of disease severity, derived from ISTAT/DRG records, cannot identify patients consuming larger resources. In liver cirrhosis, the DRG system could be improved by introducing parameters, such as Child-Pugh score, directly taking into account disease severity.

To assess the characteristics of chronic hepatitis in hepatitis B surface antigen (HBsAg) carriers with intrahepatic delta antigen, the hepatic histologic findings of 137 patients were reviewed; 101 patients were followed for 2 to 6 years. The predominant liver disease was chronic active hepatitis in 93 patients or cirrhosis in 32; minor forms of chronic persistent or lobular hepatitis were seen in 12 patients. Eight of the 26 patients with an initial diagnosis of cirrhosis died during the follow-up period. Cirrhosis developed in 31 of 75 patients (41%) without nodular regeneration seen in the first biopsy specimen; 5 of these patients died. Treatment with prednisone or azathioprine did not induce histologic amelioration of delta hepatitis or prevent cirrhosis. Chronic HBsAg hepatitis with intrahepatic expression of the delta antigen is an active, progressive disease unresponsive to conventional immunosuppressive treatment.

We report a prospective study on infants born to hepatitis B surface antigen (HBsAg) carrier mothers to estimate the incidence of perinatal transmission of HBV and HBV-associated delta agent in Northern Italy. The risk of infection to the infant was related to the presence of the HBe antigen-antibody system, HBV-specific DNA polymerase activity and antibody to delta in maternal sera, and to the titer of anti-HBe in babies at birth. The data of this study indicate: 1. Babies born to HBsAg carrier mothers with HBeAg in serum are at extremely high risk of acquiring HBV infection and of developing a chronic carrier state, whereas those born to anti-HBe-positive mothers are at a lower (P less than .01) yet consistent risk of infection. 2. HBs antigenemia is usually prolonged and symptomatic in babies born to HBeAg-positive mothers while being self-limited and asymptomatic in babies born to anti-HBe-positive mothers. 3. DNA polymerase activity in maternal serum appears to be the most sensitive marker predicting HBV transmission to the infant since it was detected in all the HBeAg-positive mothers and also in two anti-HBe-positive mothers and in one HBeAg/anti-HBe-negative mother who transmitted infection to their babies. 4. High titers of anti-HBe (up to 1:103) do not prevent HBV infection. 5. Vertical transmission of delta infection seems to occur only in circumstances that permit perinatal transmission of HBV infection.

Infection with the hepatitis B surface antigen (HBsAg)-associated delta agent (delta) was determined in a series of Italian patients with a diagnosis of acute hepatitis B (HBsAg-positive) progressive to chronicity. Twenty-two of 27 (81%) and 12 of 18 (67%) patients collected, respectively, in Naples and Cagliari, where delta is highly endemic, developed immunoglobulin M antibody to delta and/or rising titers of immunoglobulin G anti-delta during the initial acute phase of the disease. In each of them, anti-delta increased to a high-titered plateau indicative of chronic delta infection. Delta markers were found in none of the 13 patients collected in Siena, where the prevalence of delta infection is low. The great majority of the patients with anti-delta and a progressive form of HBsAg-positive hepatitis lacked the IgM antibody to hepatitis B core antigen. They were presumably unrecognized carriers of HBsAg who became infected by delta and developed hepatitis induced by this agent. In areas where delta is endemic, it may represent the true cause of seemingly type B hepatitis progressing to chronic HBsAg-positive liver disease.

To assess the epidemiology of infection with the delta agent associated with hepatitis B virus, sera from 1314 carriers of the hepatitis B surface antigen (HBsAg) and 687 patients with hepatitis B collected in 1978-1981 from different regions of Italy were tested for delta antigen and antibody to the antigen (anti-delta), and the characteristics of delta-positive patients were analyzed. Anti-delta was found in each center participating in the study, indicating that delta infection has spread throughout Italy. Its prevalence was higher in carriers in southern Italy and in those with chronic hepatitis. In northern Italy, delta infection predominated among southern emigrants in industrial towns but also among parenteral drug addicts with hepatitis B virus infection. The prevalence of delta markers was variable and generally low in acute hepatitis B, suggesting that in Italy self-limited forms of delta infection occur sporadically or by limited outbreaks. Delta infection appears to be endemic in southern Italy but a new epidemiologic event in northern Italy, where it was probably introduced by southern emigrants and is presently exceeding its ethnic confinement to spread selectively in communities of drug addicts. Presumably, the endemicity of delta is maintained by transmission of this agent from carrier to carrier of the HBsAg.

To assess the epidemiological and pathogenic effects of infection with the hepatitis-B-virus (HBV)-associated delta agent in addicts who take drugs parenterally, 225 symptomless addicts from Italy and 261 addicts with HBsAg-positive hepatitis from Italy, Denmark, Switzerland, and Ireland were tested for delta antigen (delta-Ag) and its antibody (anti-delta) by radioimmunoassay. 79 liver biopsy specimens from HBsAg-positive addicts were also tested for intrahepatic delta-Ag by immunofluorescence. Anti-delta was found in 9 (27%) of 33 of the symptomless HBsAg-positive addicts, in 13 (8%) of 156 of those without HBsAg but with anti-HBs, and in none of those negative for HBV markers. The prevalence of serum delta-Ag or anti-delta among addicts with HBsAg-positive hepatitis was 64% (104/161) in Italy, 44% (8/18) in Denmark, 33% (11/33) in Switzerland, and 31% (15/49) in Ireland. 32 of the 79 (40%)liver biopsy specimens from HBsAg-positive addicts showed positive delta-Ag immunofluorescence. Delta infection occurring simultaneously with HBV infection is common and possibly a major cause of liver disease in drug addicts who receive drug parenterally. The spread of delta infection in drug-using communities is not confined to one country, and the drug habit may represent the major means by which delta agent spreads in areas of the Western world where this infection is not endemic.

Serum or liver markers of hepatitis delta virus (HDV) infection were found in 20 of 22 (90%) Italian patients presenting with an ostensible type B hepatitis that ran an accelerated course to cirrhosis. The features of the illness conformed to a syndrome of HDV infection in young males carrying the hepatitis B surface antigen (HBsAg); a latent HBsAg state was documented in many patients by a history of prior exposure to the hepatitis B virus (HBV) or by the absence of IgM antibodies to the HB core antigen. Characteristic of the disease were the clinical overture as a severe hepatitis, the lobular involvement by an extensive necroinflammatory reaction, the exuberant expression of intrahepatic hepatitis delta antigen and an atypical HBV profile of inactive infection or accelerated seroconversion from HBeAg to anti-HBe. Superimposed upon HBV infection, HDV may create a rapidly progressive course which resembles very aggressive hepatitis B but is infrequently observed in hepatitis B alone.