Radiotherapy for the treatment of thyroid eye disease-a prospective comparison: Is orbital radiotherapy a suitable alternative to steroids?

BACKGROUND AND AIMS: To evaluate the efficacy of orbital radiotherapy (OR) for the treatment of thyroid eye disease (TED). METHODS: Thirty-five consecutive patients with active TED with contraindications to steroid therapy received a course of OR. Bilateral retrobulbar irradiation was performed with a total dose of 20 Gy. 7-points clinical activity score (7-CAS), ocular motility, visual acuity (VA), exophthalmos and eyelid retraction were prospectively evaluated at 3, 6 and 12 months and compared with baseline data. RESULTS: There was a statistically significant improvement in 7-CAS at 3, 6 and 12 months post-treatment (p < 0.05). Ocular motility disturbances improved at 6 and 12 months (p < 0.05). Visual acuity remained stable; there was no significant change in exophthalmos (mean 24 mm, SD 3 mm) or eyelid retraction (marginal reflex distance mean 6 mm, SD 1.5 mm) during the follow-up period. No side effects were registered. CONCLUSIONS: This study suggests that OR might be effective in reducing 7-CAS and ocular motility disturbances. No significant improvement in proptosis or eyelid retraction should be expected from this treatment. OR might be considered a suitable alternative treatment in TED for patients who cannot tolerate steroids.

A randomised study of hydro-jet vs. needle injection for lifting colorectal lesions prior to endoscopic resection.

BACKGROUND: Submucosal lifting of lesions prior to endoscopic resection is crucial to reduce complications and improve the technical feasibility of the procedure. AIM: To compare a self-assembled hydro-jet system vs. standard needle injection for tissue elevation prior to endoscopic resection of colorectal lesions. METHODS: Randomised study performed at a single tertiary care institution. Consecutive patients with colonoscopic diagnosis of sessile polyps or non-polypoid lesions >5 mm or laterally spreading tumours. OUTCOME MEASURES: successful elevation, time to proper elevation, completeness of excision, cautery damage, and general histological diagnostic quality (blinded pathologic assessment). RESULTS: 79 patients were randomised to hydro-jet (40 patients, group A) and needle (39 patients, group B) elevation. Successful elevation was achieved in 97.5% and 94.8%, respectively. Time to proper elevation was 8+/-5 s vs. 18+/-3 s (p<0.05). In group A, histology showed selective accumulation of fluid in the submucosa with intact collagen fibres. Damage to muscularis mucosa was never noted in the specimens of group A and in 7 cases of group B (p<0.01). Artefacts from "cautery effect" were very limited. Radial margins of resection could be adequately evaluated in all cases and were negative. CONCLUSIONS: The hydro-jet system is as effective and safe as standard needle injection for tissue elevation prior to endoscopic resection of colorectal lesions, but it is significantly faster.

Occult hepatitis B virus infection in a cohort of HIV-positive patients: correlation with hepatitis C virus coinfection, virological and immunological features.

BACKGROUND: An evaluation of the prevalence of occult hepatitis B virus (HBV) infection in HIV-positive individuals is important as HBV infection may have an impact on the outcome of the liver disease in these patients. MATERIALS AND METHODS: Of the 1,593 HIV-positive subjects enrolled in the Italian Cohort Naïve Antiretroviral (ICONA) program, 175 (10.9%) were selected for inclusion in the study on the basis of hepatitis B surface antigen (HBsAg) negativity and antibody to hepatitis B core antigen (anti- HBc) positivity; 101/175 (58%) were also anti-hepatitis C virus (HCV) positive. HBV-DNA was detected in plasma using a highly sensitive PCR assay (detection limit: 2.6 copies/ml). Two different genomic regions were assayed. Quantification was performed by real-time PCR. The HBV genotype was determined in 20 cases with occult HBV infection. Data on the antiretroviral therapy (ART) regimen was obtained in 169 individuals: 53 (31.4%) patients were ART-naive, 46 (27.2%) were under ART without lamivudine or tenofovir, and the remaining 70 (41.4%) were under ART including lamivudine or tenofovir. RESULTS: 27/175 (15%) patients had detectable HBV-DNA in their plasma: 21/101 (21%) were anti-HCV positive and 6/74 (8%) were anti-HCV negative. Genotype D was invariably found in the 20 cases analyzed. Occult HBV infection was significantly higher in HCV-coinfected subjects: adjusted OR 5.02, 95% CI 1.31-19.26, p = 0.02. The value was not associated with immune status, HIV load, or ART regimen. CONCLUSIONS: In relation to the high prevalence of occult HBV infection, particularly in HIV/HCV-coinfected individuals, it is necessary to clarify the clinical impact of this cryptic infection by monitoring HBV-DNA in plasma using the correct approach. Similarly to HBsAg-positive individuals of the Mediterranean area, HBV genotype D is invariably detected in this cohort of HIV-infected patients with occult HBV infection.

Acrylate glue injection for acutely bleeding oesophageal varices: A prospective cohort study.

BACKGROUND: Acrylate glue injection is seldom performed in patients with bleeding oesophageal varices. AIM: To assess efficacy and safety of acrylate glue injection in patients with bleeding oesophageal varices, as well as the impact of this technique on subsequent variceal ligation. METHODS: Prospective study on 133 consecutive cirrhotic patients treated by intravariceal injection of undiluted N-butyl-2-cyanoacrylate into the bleeding varix. Outcome measures were initial haemostasis, recurrent bleeding, complications and mortality at 6 weeks. RESULTS: 52 patients were actively bleeding at endoscopy and 81 showed stigmata of recent haemorrhage. Initial haemostasis was achieved in 49/52 active bleeders (94.2% [95% CI 85.1-98.5]). Overall, early recurrent bleeding occurred in 7 patients (5.2% [95% CI 2.3-10.1]). No major procedure-related complication was recorded. At 6 weeks, death occurred in 11 patients, with an overall bleeding-related mortality of 8.2% [95% CI 5.8-15.3]. Mortality was higher in active (15.4% [95% CI 6.9-28.1]) than non-active bleeders (3.7% [95% CI 0.8-10.4], OR 4.7 [95% CI 1.05-28.7], p=0.02). Of those surviving the first bleeding episode, 112 patients subsequently underwent ligation. No technical difficulties were encountered in performing the banding procedure which was successfully completed in all cases. CONCLUSIONS: Emergency injection of acrylate glue is safe and effective for the treatment of acute bleeding oesophageal varices and does not hamper subsequent variceal ligation.

Endocytoscopy can identify dysplasia in aberrant crypt foci of the colorectum: a prospective in vivo study.

BACKGROUND AND STUDY AIM: A catheter-type endocytoscope has recently been developed that is able to provide in vivo cellular images of gastrointestinal mucosa. Aberrant crypt foci (ACF) represent the earliest precursor of colorectal cancer featuring the dysplasia-carcinoma sequence. The aim of the current study was to assess the potential of the endocytoscopy system (ECS) in the "in vivo" detection of dysplasia in colorectal ACF. PATIENTS AND METHODS: Consecutive patients with colorectal ACF were studied with endocytoscopy. Blinded endoscopic and histological assessments were obtained. Lesions were excised en bloc for histology. RESULTS: A total of 48 colorectal lesions were examined in 41 patients. The mean duration of the ECS procedure was 44 +/- 12 minutes (range 31 - 62 minutes). The quality of ECS images was rated as good in 39/48, medium in six, and poor in three (6.2 %). It was possible to observe lesions at the cellular level and evaluate both cellular and structural atypia in vivo. In normal mucosa, crypts had preserved individuality and round-shaped contours. Nuclei were located at the basal third of the crypt in a single line, and the lumen was circular. In dysplastic ACF, crypt contours were polygonal, cell nuclei were elongated with pseudostratification toward the luminal half of the crypt and irregularly arranged, and the lumen was linear. In all, 23 endocytoscopic images were labeled as dysplastic and 25 as nondysplastic. Histology confirmed low-grade dysplasia in 21/23 cases (91.4 % sensitivity). Absence of dysplasia was confirmed in the remaining 25 cases (100 % specificity). Interobserver agreement between trained endoscopist and pathologist was good (wK 0.68; 95 % CI 0.59 - 0.78). CONCLUSIONS: Endocytoscopy provides real-time histological images in vivo, with clear visualization of cellular details and features of dysplasia in colorectal ACF.

Predictive value of magnification chromoendoscopy for diagnosing invasive neoplasia in nonpolypoid colorectal lesions and stratifying patients for endoscopic resection or surgery.

BACKGROUND AND STUDY AIMS: In nonpolypoid colorectal lesions, the presence of irregular, distorted glands in the colon (a disrupted crypt pattern) on magnification chromoendoscopy (MCE) is strongly associated with submucosal invasive cancer. The aim of the present study was to evaluate the ability of MCE to differentiate between an invasive crypt pattern and a noninvasive crypt pattern, including nonneoplastic lesions, and to assess the ability of this MCE classification to predict invasiveness and allow patients to be selected for endoscopic resection or surgical resection. PATIENTS AND METHODS: In a prospective study including 1560 colonoscopies, 153 flat or depressed colorectal lesions were evaluated with MCE among 534 colorectal lesions; the remainder had a polypoid appearance. The pit pattern was classified as nonneoplastic (type II) or neoplastic (types III - V), and the latter was subdivided into noninvasive (types III or IV) or submucosally invasive (type V). Lesions with a nonneoplastic and noninvasive neoplastic appearance were resected endoscopically if technically feasible, whereas those with a type V pattern were resected surgically. The resection specimens were analyzed histologically in relation to the Vienna classification. RESULTS: Using this management strategy based on the pit pattern, 86 % (n = 70) of the type II lesions were hyperplastic; the remaining 11 had low-grade intraepithelial neoplasia. Type III and IV lesions (n = 58) represented either low-grade or high-grade intraepithelial neoplasia in 95 % of the cases. Three patients had sm1 (n = 2) or sm2/3 invasive cancers. Among the patients with type V lesions (n = 14), 11 had invasive cancers (four sm1 and seven sm2/3). Endoscopic differentiation based on the pit pattern thus had a positive predictive value (PPV) of 86 % and a negative predictive value of 96 % for distinguishing between nonneoplastic and neoplastic lesions. The pit pattern criteria for distinguishing between invasive and noninvasive neoplasia (including nonneoplastic lesions), and hence the choice between endoscopic and surgical resection, had a PPV of 79 % and a NPV of 98 %. Excluding nonneoplastic lesions, the NPV would be 95 %. CONCLUSIONS: The endoscopic pit pattern on MCE has only a moderate predictive value for nonneoplastic lesions, so that leaving these flat hyperplastic lesions in place on the basis of the endoscopic magnification appearance alone cannot be generally recommended. However, MCE has a good predictive value for guiding management toward either endoscopic resection (if technically feasible) or surgical resection.

Meta-analysis: capsule enteroscopy vs. conventional modalities in diagnosis of small bowel diseases.

BACKGROUND: Prospective trials support the role of capsule enteroscopy as an improvement in diagnosing mucosal lesions in the small bowel. AIM: To determine the diagnostic yield and safety of capsule enteroscopy vs. alternative diagnostic modalities (such as push enteroscopy, small bowel follow-through or enteroclysis) in patients with small bowel diseases. METHODS: A search for prospective studies comparing capsule enteroscopy vs. other diagnostic tests in adults was performed between 1966 and 2005. Selected articles were included in a meta-analysis. Three analyses were run separately, all included studies and studies having occult gastrointestinal bleeding or Crohn's disease as main outcome. RESULTS: Seventeen studies (526 patients) met inclusion criteria. The rate difference (i.e. the absolute pooled difference in the rate of positive findings) between capsule enteroscopy and alternative modalities for small bowel disease was 41% (95% CI 35.6-45.9); 37% (95% CI 29.6-44.1) for occult gastrointestinal bleeding; and 45% (95% CI 30.9-58.0) for Crohn's disease. Failure to visualize the caecum occurred in 13%, significantly more often in occult bleeders (17%) than in patients with Crohn's disease (8%) (P < 0.006). Adverse events were recorded in 29 patients (6%). Capsule retention was more frequent in patients with Crohn's disease (3% vs. 1%, OR 4.37). CONCLUSIONS: Capsule enteroscopy proved significantly superior to push enteroscopy and small bowel radiology in the diagnosis of ileal diseases. Capsule enteroscopy is safe, though prior radiology is still necessary to rule out small bowel strictures in patients with known or suspected Crohn's disease.

Long-term outcome of argon plasma coagulation therapy for bleeding caused by chronic radiation proctopathy.

BACKGROUND: Radiation-induced proctopathy is a serious complication of radiation therapy for pelvic malignancy. AIM: To assess the safety and efficacy of argon plasma coagulation in the treatment of haemorrhagic radiation-induced proctopathy. PATIENTS: Twenty-four patients with rectal bleeding due to radiation-induced proctopathy were prospectively enrolled in the study. METHODS: Indications for treatment were iron deficiency anaemia (n = 16) and persistent bleeding, despite pharmacotherapy (n = 8). Argon flow and power used were 0.8-1.2 l/min and 40 W, respectively. An interval of at least 4 weeks was allowed between treatment sessions. Haemoglobin level, bleeding severity score, number of admissions and transfusion requirements were recorded after endoscopic coagulation and before 12 and 24 months. RESULTS: A median of 2.5 therapeutic sessions per patient were performed (range 1-6). All patients reported clinical improvement and/or cessation of rectal bleeding. The mean value of the bleeding severity score decreased from 2.9 to 0.8 (P < 0.01), while average haemoglobin levels increased by a mean of 1.9 mg/dl at the end of the treatments (P < 0.05). During a minimum follow-up of 24 months (range 24-60), rectal bleeding recurred in two cases and was successfully retreated endoscopically. One patient developed a recto-vaginal fistula. CONCLUSIONS: Argon plasma coagulation appears to be a safe and effective technique for management of rectal bleeding caused by radiation-induced proctopathy.

Treatment of blepharospasm with botulinum neurotoxin type A: long-term results.

PURPOSE: To describe the long-term efficacy and side effects of treatment of blepharospasm with botulinum neurotoxin type A (Botox). METHODS: A total of 178 patients with blepharospasm were treated by injections of botulinum toxin in the Eye Clinic of the University of Naples from 1980 to 2001. The severity of spasm for each patient was graded on a four-point scale. Duration of improvement was assessed and reported in months. RESULTS: Of 178 cases, 10 were lost to follow-up; of the remaining patients, 93% reported improvement after treatments. The mean duration of improvement was 3.6 months. Twelve patients (76%) who underwent more than 14 treatments maintained stable relief. Three patients (1.7%) had a total remission of spasms. Side-effects were local; none of the 168 patients experienced any systemic or toxic reaction. CONCLUSIONS: Botulinum toxin therapy for blepharospasm can provide long-lasting relief and reduction of spasms in the majority of patients. This therapy has the advantages of being safe, simple, and repeatable.

When to start highly active antiretroviral therapy in chronically HIV-infected patients: evidence from the ICONA study.

OBJECTIVES: To compare the response to highly active antiretroviral therapy (HAART) in individuals starting HAART at different CD4 cell counts. DESIGN: The mean increase in CD4 cell count and rate of virological failure after commencing HAART were measured in antiretroviral-naive patients (1421) in a large, non-randomized multicentre, observational study in Italy (ICONA). Clinical endpoints were also evaluated in a subset of patients who started HAART with a very low CD4 cell count. RESULTS: After 96 weeks of therapy, the mean rise in CD4 cell count was 280, 281 and 186 x 10(6) cells/l in patients starting HAART with a CD4 cell count < 200, 201--350 and > 350 x 10(6) cells/l, respectively. Patients starting HAART with a CD4 cell count < 200 x 10(6) cells/l tended to have a higher risk of subsequent virological failure [relative hazard (RH), 1.15; 95% confidence interval (CI), 0.93--1.42] compared with patients starting with > 350 x 10(6) cells/l. There was no difference in risk between the 201--350 and the > 350 x 10(6) cells/l groups (RH, 1.0; 95% CI, 0.79--1.29). The incidence of new AIDS-defining diseases/death in patients who started HAART with a CD4 count < 50 was 0.03/person-year (95% CI, 0.10--0.33) during the time in which the patient's CD4 cell count had been raised to > 200 x 10(6) cells/l. CONCLUSIONS: There was no clear immunological or virological advantage in starting HAART at a CD4 cell count > 350 rather than at 200--350 x 10(6) cells/l. The increase in CD4 cells restored by HAART is meaningful in that they are associated with reduced risk of disease/death.

Endoclips versus heater probe in preventing early recurrent bleeding from peptic ulcer: a prospective and randomized trial.

BACKGROUND: Endoscopic application of hemoclips (HC) was prospectively compared with heat probe (HP) treatment in patients with bleeding ulcers. METHODS: One hundred thirteen patients with major stigmata of ulcer hemorrhage were randomly assigned to receive HP (n = 57) or HC (n = 56). Clinical and endoscopic features were comparable in both groups. Recurrent bleeding was retreated with the modality previously used. Patients in whom treatment or retreatment was unsuccessful underwent emergency surgery. RESULTS: Hemostasis, adequate treatment of visible vessel, 30-day mortality, and emergency surgery rates were similar for both groups. Recurrent bleeding was 21% for HP and 1.8% for HC (p < 0.05). Length of hospital stay and transfusion requirements were significantly lower in the HC group. There was no evidence of clip-induced tissue injury or impaired ulcer healing. Clips dislodged spontaneously in most patients within 8 weeks of treatment. No further hemorrhage occurred on a median follow-up of 11 months (range 1-23). CONCLUSIONS: The hemoclip is safe and effective in the treatment of severe ulcer bleeding and is superior to HP in preventing early recurrent bleeding.

Endoscopic clipping of perforation following pneumatic dilation of esophagojejunal anastomotic strictures.

Two patients with small perforations occurring after endoscopic balloon dilation of esophagojejunal anastomotic strictures were treated conservatively using metal clips. Closure of the perforation was achieved in both cases, using one and two clips in a single session. There was no procedure-related morbidity and no patient developed complications. Patients were discharged from hospital on days 4 and 5, respectively. In patients with esophagojejunal anastomotic strictures, endoscopic treatment of postdilation perforation by metal clips is safe and effective.

Prospective comparison of argon plasma coagulator and heater probe in the endoscopic treatment of major peptic ulcer bleeding.

BACKGROUND: Argon plasma coagulator was prospectively compared with heater probe in patients with bleeding peptic ulcers. METHODS: Forty-one patients with major stigmata of ulcer hemorrhage were randomly assigned to receive either heater probe (n = 20) or argon plasma coagulation (n = 21) treatment; 40% had active bleeding and 60% had a nonbleeding visible vessel in the ulcer crater. The two groups were similar with respect to all background variables. Episodes of recurrent bleeding were retreated with the same modality as used previously. Patients in whom treatment or retreatment failed underwent emergency surgery. RESULTS: Initial hemostasis (95% vs. 95.2%), recurrent bleeding (21% vs. 15%), 30-day mortality (5% vs. 4.7%), and emergency surgery (15% vs. 9.5%) were comparable in the heater probe and argon plasma coagulation groups, respectively. Argon plasma coagulation provided faster hemostasis (mean 60 +/- 19 vs. 115 +/- 28 seconds, p < 0.05). CONCLUSIONS: Argon plasma coagulation is safe and effective. Larger studies in patients with bleeding peptic ulcers are needed to confirm these promising results.

Emergency endoscopic ligation of actively bleeding gastric varices with a detachable snare.

BACKGROUND: Bleeding gastric varices (BGV) is a challenging condition whose management remains controversial and often empirical. METHODS: Over the past 6 months, emergency ligation of BGV was performed in seven cirrhotic patients (five men, two women; age range 47 to 70 years) using a detachable snare. Child's grade was B in two and C in five patients. Two patients had a concurrent hepatocellular carcinoma. Three patients had been previously treated with either balloon tamponade or injection sclerotherapy for bleeding esophageal varices. RESULTS: Hemostasis was achieved in all patients. Morbidity consisted of fever in one case. Six snares passed spontaneously, one was removed from the stomach on follow-up examination. Post-ligation ulcers were detected in all patients after treatment (mean diameter 7.4+/-2.1 mm) with no stigmata of recurrent hemorrhage. No early rebleeding was observed during hospital stay. On a mean follow-up of 3.8 months (range 2 to 6 months), no digestive hemorrhage was recorded. Ligated gastric varices were significantly 'reduced in size in four patients. CONCLUSIONS: Emergency ligation with detachable snare is feasible and may be an alternative life-saving method of endoscopic hemostasis in BGV.

Endoscopic mechanical lithotripsy of difficult common bile duct stones.

BACKGROUND: Mechanical lithotripsy for the management of difficult common bile duct stones has sometimes yielded conflicting results. METHODS: A series of 162 consecutive patients who underwent mechanical lithotripsy was evaluated retrospectively and a large number of variables tested for their association with successful outcome. RESULTS: The procedure was safe (morbidity rate 1.8 per cent) and effective (84.0 per cent stone clearance rate). Univariate and multivariate analysis showed that stone size was the only outcome predictor (mean(s.d.) diameter of grasped versus non-grasped stones 21.7 (6.7) versus 28.3(10.4) mm; F = 10.72, 98 d.f., P = 0.002). The cumulative probability of bile duct clearance ranged from over 90 per cent for stones with a diameter less than 10 mm to 68 per cent for those greater than 28 mm in diameter (P < 0.02). CONCLUSION: Patients at high risk of lithotripsy failure (stone diameter of 28 mm or more) might more wisely undergo surgery or other non-surgical procedures, such as extracorporeal shock-wave lithotripsy or long-term biliary stenting.

[Rhodococcus equi infections in AIDS: personal cases]. / Sepsi da Rhodococcus equi in corso di AIDS: osservazioni personali.

We report on the occurrence of an uncommon pathogen, Rhodococcus equi (R.e.) in HIV infection. In the period february 1990-July 1991 we performed the diagnosis of R.e. infection (lung, lung-central nervous system) in two infected patients, aged 27 and 31 years, both males, drug addicts, classified as CDC IV. In the first of them an cavitating right bronchopneumonia (bpm) was diagnosed as of tuberculous origin, on the ground of the microscopic demonstration of an acid-fast, gram-positive strain in b.a.l.. A standard antituberculous regimen was uneffective and R.e. was eventually isolated in three blood culture taken shortly before the exitus and at post-mortem examination of the lungs. In the second patient a subclavian right bpm developed without microbiological evidence of any common pathogen. A third-generation cephalosporin course was only partially successful (clinical amelioration, incomplete clearing of radiological findings). After 3 months the patient relapsed and an aseptic meningitis developed. Cultures of blood and csf yielded a R.e. strain; post-mortem examination revealed a diffuse, cavitating bpm. Our personal experience underlines the difficulty in recognizing R.e. infections in compromised host, because of similarity to other entities (i.e. tuberculosis) and the absence of pathognomonic hints.

Different expression of HLA class I antigens in liver of children with chronic hepatitis B, evaluated by immunohistochemical method.

Studies on the quantitative expression of the Major Histocompatibility Complex (MCH) in hepatocytes chronically infected by Hepatitis B Virus (HBV) report that an increased expression of these antigens could be related to a good immunological response. In the present work we analyze the expression of the MCH antigens in cryostatic sections of liver biopsies taken from subjects (19 children) with various forms of HBsAg positive chronic hepatitis. A high expression of HLA class I antigens and a high degree of hepatocyte necrosis was evident in Chronic Active Hepatitis (CAH) and Chronic Lobular Hepatitis (CLH). On the contrary, subjects with histological diagnosis of Chronic Persistent Hepatitis (CPH) showed a low expression of such antigens. There was however, the difference that in subjects with high hepatic cytolysis and high expression of HLA class I antigens, serum HBV-DNA was clearly present in almost all the cases with CAH, but not detectable in all cases with CLH. The expression of HLA class II antigens and of Beta2 microglobulin was the same in all 19 cases. All cases with HBV-DNA positivity with high class I antigen expression had active hepatitis which seems to suggest that all attempts at viral clearance on the part of the immune system have been in vain. We hope our paper will be an additional parameter for evaluating the course of hepatitis during Interferon treatment.

Chronic hepatitis in childhood: the spectrum of the disease.

During a multicentre study of chronic hepatitis in childhood diagnosed by biopsy, the spectrum of the disease has been evaluated in 196 consecutive patients, including 157 from Northern Italy and 39 from Southern Italy. Only 31% of patients in the former group and 27% in the latter were symptomatic when first seen: the majority of cases being seen after familial screenings for hepatitis B virus (HBV) markers or during intercurrent infections, thus suggesting that the frequency of chronic hepatitis in childhood might be largely underestimated in our area. In Southern and Northern Italy 83% of symptomatic and 95% of asymptomatic patients were hepatitis B surface antigen (HBsAg) positive in serum; only 15 (8.3%) of these children were born to mothers known to be HBsAg positive at delivery, but a high circulation of HBV was found in their families: in fact more than 65% of household contacts in Northern Italy and more than 90% in Southern Italy had serological evidence of past or ongoing HBV infection. These data indicate that, although familial screenings for HBV could have enhanced the percentage of HBsAg positive asymptomatic cases, chronic hepatitis in Italian children is mainly caused by HBV infection acquired in the familial setting through horizontal transmission. Such findings also emphasise the importance of mass vaccination of infants as the most effective means to prevent chronic type B hepatitis in childhood in our area. Among HBsAg positive children 55% had histological features of chronic active hepatitis and 85% were hepatitis Be antigen (HBeAg) positive in serum. Anti-HBe positive hepatitis was significantly more frequent in Southern than in Northern Italy in parallel with the significantly higher prevalence (17%) of hepatitis delta virus infection in that area. Of the 16 HBsAg negative cases included in the study three had autoimmune hepatitis, three Wilson's disease, one alpha1 antitrypsin deficiency, and nine had cryptogenic hepatitis, often associated to mild liver lesions resembling those seen in our adult patients with chronic non-A, non-B hepatitis unrelated to percutaneous exposure.